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Twitch and tetanic force responses and longitudinal propagation of action potentials in skinned skeletal muscle fibres of the rat.

1. Transverse electrical field stimulation (50 V cm-1, 2 ms duration) of mechanically skinned skeletal muscle fibres of the rat elicited twitch and tetanic force responses (36 +/- 4 and 83 +/- 4 % of maximum Ca2+-activated force, respectively; n = 23) closely resembling those in intact fibres. The responses were steeply dependent on the field strength and were eliminated by inclusion of 10 microM tetrodotoxin (TTX) in the (sealed) transverse tubular (T-) system of the skinned fibres and by chronic depolarisation of the T-system. 2. Spontaneous twitch-like activity occurred sporadically in many fibres, producing near maximal force in some instances (mean time to peak: 190 +/- 40 ms; n = 4). Such responses propagated as a wave of contraction longitudinally along the fibre at a velocity of 13 +/- 3 mm s-1 (n = 7). These spontaneous contractions were also inhibited by inclusion of TTX in the T-system and by chronic depolarisation. 3. We examined whether the T-tubular network was interconnected longitudinally using fibre segments that were skinned for only approximately 2/3 of their length, leaving the remainder of each segment intact with its T-system open to the bathing solution. After such fibres were exposed to TTX (60 microM), the adjacent skinned region (with its T-system not open to the solution) became unresponsive to subsequent electrical stimulation in approximately 50 % of cases (7/15), indicating that TTX was able to diffuse longitudinally inside the fibre via the tubular network over hundreds of sarcomeres. 4. These experiments show that excitation-contraction coupling in mammalian muscle fibres involves action potential propagation both transversally and longitudinally within the tubular system. Longitudinal propagation of action potentials inside skeletal muscle fibres is likely to be an important safety mechanism for reducing conduction failure during fatigue and explains why, in developing skeletal muscle, the T-system first develops as an internal longitudinal network.

Action Potentials↗

Responses of the longitudinal muscle and the muscularis mucosae of the rat duodenum to adenine and uracil nucleotides.

1. Previous studies have shown that the rat duodenum contains P1 and P2Y purinoceptors via which it relaxes to adenosine and adenosine 5'-triphosphate (ATP) respectively. It has also been shown to contract to uridine 5'-triphosphate (UTP) and adenosine 5'-O-(3-thiotriphosphate) (ATP-gamma-S), and based on their differential inhibition by the P2 antagonist suramin it has been suggested that they act via two separate receptors. In addition, the rat duodenum has been shown to dephosphorylate ATP rapidly via ectonucleotidases and adenosine deaminase. In this study the responses of two preparations from the rat duodenum, the longitudinal muscle and the muscularis mucosae, were investigated using a series of nucleotides and suramin. 2. 2-Methylthioadenosine 5'-triphosphate (2-MeSATP), ATP, ATP-gamma-S and adenosine 5'-alpha,beta-methylene-triphosphonate (AMPCPP) each relaxed the longitudinal muscle, with an agonist potency order of 2-MeSATP > ATP = ATP-gamma-S > AMPCPP, while UTP and uridine 5'-diphosphate (UDP) were not observed to elicit relaxation. This indicates the presence of a relaxant P2Y-purinoceptor on the longitudinal muscle. The longitudinal muscle did not contract to any of the agonists at concentrations of 300 microM, apart from ATP-gamma-S which caused very weak contractions. 3. ATP-gamma-S, adenosine 5'-methylenediphosphonate (AMPCP), AMPCPP, ATP, UTP, adenosine 5'-diphosphate (ADP), UDP and 2-MeSATP each contracted the muscularis mucosae with an agonist potency order of ATP-gamma-S > or = AMPCP > or = AMPCPP = ATP = UTP = ADP = UDP >> 2-MeSATP, although maximal responses were not obtained at concentrations of 300 microM. The muscularis mucosae did not relax to any of the agonists at concentrations of 300 microM. 4. Suramin (1 mM) inhibited relaxations induced by ATP on the longitudinal muscle, shifting the relaxation concentration-response curve to the right. This further supports the presence of a P2Y-purinoceptor on this muscle layer. Suramin (1 mM) inhibited contractions induced by AMPCPP, but not those induced by ATP, UTP or ATP-gamma-S, in the muscularis mucosae. Desensitization of the muscularis mucosae was seen with AMPCPP, but not with UTP or ATP-gamma-S, and no cross-desensitization between AMPCPP and UTP or ATP-gamma-S was observed. This suggests there are two receptors which mediate contraction on the rat duodenum muscularis mucosae, one suramin-sensitive and the other suramin-insensitive. 5. ATP was rapidly degraded by the muscularis mucosae to ADP, adenosine 5'-monophosphate (AMP) and inosine, with no adenosine being detected. A similar rate of degradation was seen for UTP with UDP, uridine 5'-monophosphate (UMP) and uridine being formed and for 2-MeSATP with 2-methylthioadenosine 5'-diphosphate (2-MeSADP), 2-methylthioadenosine 5'-monophosphate (2-MeSAMP) and 2-methylthioadenosine being formed. AMPCPP and ATP-gamma-S were both degraded more slowly, AMPCPP being degraded to AMPCP, and ATP-gamma-S to ADP, AMP and inosine. Suramin (1 mM), did not significantly affect the rate and pattern of degradation of these nucleotides, apart from AMPCPP which was degraded slightly more slowly in the presence of suramin. 6. These results show that there is a P2Y-purinoceptor which mediates relaxation in the rat duodenum longitudinal muscle. They also show that there is a contraction-mediating suramin-sensitive receptor on the rat duodenum muscularis mucosae which is desensitized by AMPCPP, and thus is probably of the P2X subtype. In addition, there is a contraction-mediating suramin-insensitive receptor on the rat duodenum muscularis mucosae which is not desensitized by UTP or ATP-gamma-S, and at which ATP and UTP show equal potency, and is thus probably of the P2U subtype. In addition, the rat duodenum muscularis mucosae contains ectonucleotidases and adenosine deaminase, which rapidly degrade nucleotides, although the inhibition by suramin of this deg

Adenosine Triphosphate↗

VIP- and PACAP-mediated nonadrenergic, noncholinergic inhibition in longitudinal muscle of rat distal colon: involvement of activation of charybdotoxin- and apamin-sensitive K+ channels.

1. The mediators of nonadrenergic, noncholinergic (NANC) inhibitory responses in longitudinal muscle of rat distal colon were studied. 2. An antagonist of pituitary adenylate cyclase activating peptide (PACAP) receptors, PACAP6-38, concentration-dependently inhibited the rapid relaxation of the longitudinal muscle induced by electrical field stimulation (EFS), resulting in a maximal inhibition of 47% at 3 microM. 3. PACAP6-38 inhibited the relaxation by 75% in the presence of the vasoactive intestinal peptide (VIP) receptor antagonist, VIP10-28 at 3 microM, which inhibited the relaxation by 44%. 4. An antagonist of large conductance Ca(2+)-activated K+ channels, charybdotoxin, concentration-dependently inhibited the rapid relaxation of the longitudinal muscle, resulting in a maximal inhibition of 58% at 100 nM. 5. An antagonist of small conductance Ca(2+)-activated K+ channels, apamin, concentration-dependently inhibited the relaxation (58% at 1 microM). 6. Treatment with both K+ channel antagonists resulted in 84% inhibition of the EFS-induced relaxation, which is comparable to the extent of inhibition induced by PACAP6-38 plus VIP10-28. 7. The inhibitory effect of VIP10-28 and of apamin, but not of charybdotoxin was additive: the same applied to PACAP6-38 and charybdotoxin, but not apamin. 8. Exogenously added VIP (100 nM 1 microM) induced a slow gradual relaxation of the longitudinal muscle. Charybdotoxin, but not apamin significantly inhibited the VIP-induced relaxation VIP10-28, but not PACAP6-38 selectively inhibited the VIP-induced relaxation. 9. Exogenously added PACAP (10-100 nM) also induced slow relaxation. Apamin and to a lesser extent, charybdotoxin, inhibited the PACAP-induced relaxation. PACAP6-38, but not VIP10-28 selectively inhibited the PACAP-induced relaxation. 10. Apamin at 100 nM inhibited inhibitory junction potentials (i.j.ps) induced by a single pulse of EFS Apamin also inhibited a rapid phase, but not a delayed phase of i.j.ps induced by two pulses at 10 Hz. VIP10-28 did not inhibit i.j.ps induced by a single pulse, but significantly inhibited the delayed phase at two pulses. A combination of apamin and VIP10-28 abolished the i.j.ps induced by two pulses. 11. Both VIP and PACAP induced slow hyperpolarization of the cell membrane of the longitudinal muscle. Apamin inhibited the PACAP-, but not VIP-induced hyperpolarization. 12. From these findings it is suggested that VIP and PACAP are involved in NANC inhibitory responses of longitudinal muscle of the rat distal colon via activation of charybdotoxin- and apamin-sensitive K+ channels, respectively.

Animals↗

Myogenic electrical control activity in longitudinal muscle of human and dog colon.

1. The myogenic electrical activities of longitudinal muscle cells of the dog and human colon were investigated using intracellular microelectrodes. 2. The resting membrane potentials of dog and human longitudinal muscle cells at the serosal side of the muscle layer were -49.4 +/- 0.9 and -44.8 +/- 1.3 mV respectively. 3. Spontaneous electrical activity consisted of electrical oscillations of 13.7 +/- 1.1 mV and 8.6 +/- 2.1 mV amplitude, and 19.8 +/- 1.0 cycles/min and 26.1 +/- 1.6 cycles/min frequency for dog and human cells respectively. 4. Spiking activity only occurred superimposed on the electrical oscillations; the mean rate of rise of spikes was approximately 150 mV/s in the dog and approximately 260 mV/s in human cells and that of the oscillations was approximately 18 mV/s in the dog and approximately 16 mV in human cells. 5. Spiking activity was abolished by calcium influx blockers and 0.01 mM-calcium Krebs solution. The amplitude of the electrical oscillations was reduced to 0.2-1.0 mV 30 min after calcium influx blockade or 30 min in 0.01 mM-calcium Krebs solution. 6. Because of the high frequency of the oscillation-spike complexes, there was summation of associated contractile events in such a way that contraction frequency corresponded to frequency of bursts of oscillations and not to the frequency of the individual oscillations. 7. The resting membrane potential of the longitudinal muscle cells at the myenteric plexus side of the layer was -44.9 +/- 1.0 mV, significantly lower than at the serosal side. 8. A gradient in membrane potential and slow-wave amplitude exists in circular muscle of dog colon, with the highest value at the mucosal side (-68.4 and 28.1 mV respectively) and the lowest at the myenteric side (-62.5 and 8.6 mV) of the muscle layer. 9. Differences between resting membrane potential and electrical activity of longitudinal and circular muscle cells of the dog colon measured at the myenteric side of both muscle layers suggests absence of electrotonic coupling between the two types of cells. 10. Similarity of resting membrane potentials of longitudinal and circular muscle of the human colon suggests possible electronic coupling. 11. Since the electrical oscillations in longitudinal muscle control occurrence of spiking activity and type of contraction, they may be called 'electrical control activity'.

Action Potentials↗

Physiological mechanisms adopted by chondrocytes in regulating longitudinal bone growth in rats.

1. Chondrocyte activities within growth plate cartilage are the principal determinants of longitudinal bone growth, and it was the aim of this investigation to assess how these cell activities are modulated under various growth rate conditions. Using proximal tibial growth plates from rats of different ages, growth rate was determined by fluorochrome labelling and incident light fluorescence microscopy. Various cellular parameters contributing to longitudinal bone growth were quantified by light microscopic stereology. The size of the proliferating cell population ('growth fraction') was estimated by autoradiography (using [3H]thymidine labelling). 2. A comparison between data for suckling (21-day-old) and fast-growing (35-day-old) rats revealed that growth acceleration is achieved almost exclusively by cell-shape modelling, namely by an increase in final cell height and a decrease in lateral diameter, whereas final cell volume and surface area are slightly reduced. Cell proliferation rate in the longitudinal direction and net matrix production per cell remain unchanged. The physiological increase in linear growth rate thus appears to be based principally upon a controlled structural modulation of the chondrocyte phenotype. On the other hand, a physiological reduction in growth rate (i.e. growth deceleration) effected during the transition from pre-puberty (35-day-old rats) to maturity (80-day-old rats) is achieved by simultaneous decreases in several chondrocyte parameters, including cell height (i.e. phenotype modulation), cell volume and proliferation rate (in the longitudinal direction). However, chondrocytes continue to produce matrix at a level comparable to that attained during the period characterized by high growth rates (i.e. at 21 and 35 days). Cartilage matrix thus appears to play a subordinate role in regulating longitudinal bone growth rate. The duration of the hypertrophic cell activity (i.e. phenotype modulation) phase remains constant (at approximately 2 days) under the various growth rate conditions. 3. The findings presented in this study indicate that measurement of bulk parameters such as [35S]sulphate incorporation into matrix components, [3H]thymidine uptake by cells and growth plate height are of limited value as estimators of longitudinal bone growth, since changes in the parameters that these measurements quantify bear little relationship to changes in linear growth rate, and may be useful only as indicators of total growth plate activity.

Aging↗

Electrical coupling of circular muscle to longitudinal muscle and interstitial cells of Cajal in canine colon.

1. Electrical communication between circular muscle, longitudinal muscle and interstitial cells of Cajal (ICC) was investigated; the hypothesis was tested that the resting membrane potential (RMP) gradient in the circular muscle of canine colon is caused by electrical coupling to neighbouring cells. 2. Isolated longitudinal muscle exhibited spike-like action potentials at a RMP of -45 mV with a frequency and amplitude of 20 cycles/min and 12 mV, respectively. 3. The circular muscle (CM), devoid of longitudinal muscle, myenteric plexus and submuscular ICC-smooth-muscle network, was electrically quiescent at a uniform RMP of -62 mV across the entire circular muscle layer. 4. Preparations consisting of only the submuscular ICC network and a few adjacent layers of circular muscle cells exhibited slow wave-type action potentials at a RMP of about -80 mV. 5. In ICC-CM preparations, consisting of the submuscular ICC network and circular muscle, a RMP gradient of 10 mV was observed near the submucosal border, whereas the RMP was constant at -62 mV in the myenteric half of the circular muscle. 6. In full thickness (FT) preparations, a RMP gradient of 23 mV was observed. The RMP decreased gradually from -71 mV at the submucosal border to -48 mV at the myenteric border of the circular muscle. 7. Coupling of longitudinal muscle to circular muscle caused circular muscle cells at the myenteric surface to depolarize by 14 mV and longitudinal muscle cells to hyperpolarize by 3 mV. 8. In the ICC-CM preparations, the slow wave amplitudes did not decay exponentially away from the ICC network indicating that slow waves propagated actively into the circular muscle; in the FT preparations there was an apparent exponential decay but this was due to the RMP gradient. 9. Spike-like action potentials (SLAPs) superimposed on the plateau phase of slow waves did not decay exponentially away from the myenteric border suggesting that SLAPs were generated within the circular muscle layer. 10. In summary, circular muscle cells possess a uniform intrinsic RMP of -62 mV. The RMP gradient in situ is caused by electrical coupling of circular muscle cells to longitudinal muscle cells and the submuscular network of ICC. In situ, slow wave-type action potentials propagate actively into the circular muscle layer, and, dependent on the level of excitation, circular muscle cells actively generate spikes.

Action Potentials↗

Agonist-activated, ryanodine-sensitive, IP3-insensitive Ca2+ release channels in longitudinal muscle of intestine.

We have previously shown that Ca2+ mobilization in longitudinal muscle is not mediated by inositol 1,4,5-trisphosphate (IP3) and depends on an obligatory influx of Ca2+. The present study examined whether Ca2+ influx activates ryanodine-sensitive Ca2+ channels to cause Ca(2+)-induced Ca2+ release. Ryanodine bound with high affinity to longitudinal muscle cells [dissociation constant (Kd) 7.3 +/- 0.3 nM] and microsomes (Kd 7.5 +/- 0.4 nM) and induced concentration-dependent 45Ca2+ efflux [50% effective concentration (EC50) 1.3 +/- 0.5 nM], increase in cytosolic free Ca2+ (EC50 2.0 +/- 0.7 nM), and contraction (EC50 0.9 +/- 0.2 nM) but had no effect in circular muscle cells. Ryanodine binding and ryanodine-induced Ca2+ release were enhanced by caffeine and inhibited by dantrolene and ruthenium red but were not affected by IP3 or heparin. Changes in Ca2+ concentration (50-500 nM) caused Ca2+ release from permeabilized longitudinal but not circular muscle cells loaded with 45Ca2+. The contractile agonist cholecystokinin-8 elicited 45Ca2+ efflux in both circular and longitudinal muscle cells; efflux in longitudinal muscle cells was abolished by Ca2+ channel blockers and by pretreatment of the cells with ryanodine. Pretreatment with thapsigargin abolished agonist-induced 45Ca2+ efflux in both cell types. We conclude that ryanodine-sensitive IP3-insensitive Ca2+ release channels with properties similar to those in cardiac muscle are present in longitudinal but not circular muscle cells of intestine and that agonist-mediated Ca2+ influx activates these channels, leading to Ca(2+)-induced Ca2+ release.

Animals↗

Electrical coupling of longitudinal and circular intestinal muscle.

Space constants (lambda) were determined for longitudinal-circular muscle strips of cat jejunum by the partition method. Pulses of hyperpolarizing current spread along the major axes of circular muscle cells. In the absence of electrical coupling lambda measured from the longitudinal side of the strips should have been approximately 20 times shorter than lambda measured from the circular side. Median values were found to be statistically the same, 2.4 mm for the longitudinal side (n = 13) and 2.9 mm for the circular (n = 25). Methyl blue, iontophoretically injected into cells on the longitudinal side after recording large hyperpolarizing responses, was found in muscle cells located superficially in the longitudinal layer. The radial lambda for longitudinal muscle, determined from the change in magnitude of the hyperpolarizing response as the microelectrode was advanced through the layer, was 0.27 mm. This is too large to cause differences in depth of recording to significantly affect the circumferential lambda in this layer. These data provide evidence for a high degree of electrical coupling between the two muscle layers of cat jejunum.

Animals↗

Longitudinal but not circumferential deformation reflects global contractile function in the right ventricle with open pericardium.

The clinical evaluation of right ventricular (RV) contractility is problematic because instantaneous RV volumetry is difficult to achieve. Our aim was to test whether global RV contractility can be assessed by using regional indexes in the longitudinal and/or circumferential axis. Six anesthetized adult ewes were instrumented with a RV conductance catheter and four RV free wall sonomicrometry crystals (interrogating the longitudinal and circumferential axes). Global and regional preload recruitable stroke work (PRSW) were measured by using acute vena cava occlusions at baseline, during esmolol and dobutamine infusion, and during stable low-preload and high-afterload conditions. The agreement between regional and global PRSW was assessed with regression and Bland-Altman analysis. Both regional PRSW indexes correlated well with global PRSW in baseline conditions, during inotropic modulation (R(2) = 0.83 and 0.74 for longitudinal and circumferential regional PRSW, respectively), and during preload reduction (R(2) = 0.62 and 0.83, respectively), but only longitudinal regional PRSW correlated with global PRSW in increased afterload conditions (R(2) = 0.59 and 0.13 for longitudinal and circumferential regional PRSW, respectively). We conclude that in the open-chest, open-pericardium animal model, deformation in the longitudinal axis accurately reflects global RV contractile function in baseline conditions and during acute load modulation, whereas circumferential motion is influenced by changes in afterload.

Adrenergic beta-Antagonists↗

Differential expression of L- and T-type calcium channels between longitudinal and circular muscles of the rat myometrium during pregnancy.

The aim of this study was to evaluate the difference in the expression of mRNA of two types of calcium channels between longitudinal and circular muscle layer of rat myometrium during pregnancy. Changes in the expressions of the mRNA encoding L-type (alpha1C) and T-type (alpha1G, alpha1H, and alpha1I) calcium channels in longitudinal and circular smooth muscle cells of the rat myometrium were examined using a comparative kinetic RT/PCR method. During the course of pregnancy, alpha1C mRNA expression showed an N-shaped change in longitudinal muscle, but simply increased after mid-pregnancy in circular muscles. The mRNAs for alpha1G and alpha1H, but not that for alpha1I, were expressed in both longitudinal and circular smooth muscle. In longitudinal muscle, the change in alpha1H mRNA was similar to that in alpha1C mRNA during gestation, but the expression of alpha1G mRNA changed significantly only at term (day 22). In circular muscle, alpha1H mRNA expression was stable at any stage during pregnancy, but alpha1G mRNA significantly increased on day 15 and at term. No relationship was observed between voltage-dependent calcium-channel mRNA expressions and either proliferation or hypertrophy of circular muscle during pregnancy. These results show (a) that during pregnancy, the expression levels of L-type channels change dynamically, and it may contribute directly to the regulation of cell excitability, and (b) that the T-subtype that increases during pregnancy differs between longitudinal and circular muscle cells, although their functions remain unclear.

Animals↗

Suppression of longitudinal versus transverse conduction by sodium channel block. Effects of sodium bolus.

BACKGROUND: Arrhythmias resulting from treatment with sodium channel-blocking antiarrhythmic drugs have been successfully treated with sodium infusion, although the mechanism underlying this effect is uncertain. METHODS AND RESULTS: In this study, we used a multielectrode array to examine the effects of O-desmethyl encainide (ODE), a potent sodium channel-blocking metabolite of encainide, on conduction in canine ventricle. ODE depressed both longitudinal and transverse conduction velocities in a plasma concentration-related fashion (r = -0.74, -0.60; p less than 0.001). At ODE concentrations less than or equal to 300 ng/ml (n = 34), conduction velocity was depressed to the same extent in the longitudinal (-21.9 +/- 8.4%, SD) and transverse orientations (-22.0 +/- 8.8%). However, at concentrations greater than 300 ng/ml (n = 17), conduction was significantly more impaired longitudinally than transversely (-44.5 +/- 11.7% versus -34.4 +/- 13.7%, p less than 0.02). In 12 animals with high concentrations (mean, 432 +/- 32 ng/ml), a 5-meq/kg bolus of sodium chloride over 1 minute immediately increased conduction velocity; this effect was significantly greater and longer lasting in the longitudinal orientation. In two animals, conduction block in the longitudinal orientation was documented at high plasma ODE and was immediately reversed by sodium bolus. CONCLUSIONS: We conclude that the major effect of sodium in animals with excess sodium channel block is improvement of longitudinal propagation; this effect may underlie the antiarrhythmic action of sodium in the analogous clinical setting.

Animals↗

What Can We Learn From Longitudinal Studies of Adult Development?

This article distinguishes between normal and pathological aging, provides an interdisciplinary context, and then considers a sample case of cognitive aging. Developmental influences on cognition include the physiological infrastructure, genetic predispositions, and environmental influences. Different types of longitudinal studies are distinguished, and contrasting findings of cross-sectional and longitudinal are examined in the sample case of the Seattle Longitudinal Study. Also considered is the longitudinal context for intervention studies and the role of longitudinal family studies in assessing rate of aging and generational differences in rates of aging. Finally, attention is given to the role of longitudinal studies in the early detection of risk for dementia in advanced age.

Journal Article↗

Cross-sectional and longitudinal relationships between alcohol consumption and lipids, blood pressure and body weight indices.

OBJECTIVE: Serum lipids, blood pressure and body mass may mediate the U-shaped relationship of alcohol consumption with type 2 diabetes mellitus and coronary heart disease. This study examines the cross-sectional and long-term longitudinal relationships of (changes in) alcohol consumption with (changes in) serum lipids, blood pressure and body mass indices. METHOD: In this prospective, observational cohort study, two measurements of alcohol consumption, serum total and high-density lipoprotein cholesterol, triglycerides, blood pressure, body weight, the thickness of four skinfolds and waist circumference were performed 4 years apart in healthy volunteers (143 men and 174 women, 32 years old at the first measurement). Alcohol consumption from beer, wine and distilled spirits was assessed using an extensive dietary history interview. Linear regression analyses were performed to study the cross-sectional relationships between the amount of alcohol consumed at the age of 32 years and the levels of the lipids, blood pressure and body weight indices, and to study the longitudinal relationships between the changes in the amount of alcohol consumed over the 4 years of follow-up and the concurrent changes in the lipids, blood pressure and body weight indices. Nonlinearity was investigated for the cross-sectional relationships. RESULTS: A 10-g/day difference in alcohol consumption was positively related with a 0.05 mmol/L (1.9 mg/dl) difference in high-density lipoprotein cholesterol in both cross-sectional (p = .004), and longitudinal (p < .0001) analyses. This relationship did not differ for men and women or for the consumption of beer, wine or distilled spirits. Relationships with changes in total cholesterol, triglycerides, systolic, diastolic, and pulse pressure, body weight and the sum of four skinfolds were not significant. A borderline significant inverse longitudinal relationship was found with waist circumference. The other lifestyle behaviors (tobacco smoking, physical activity and dietary habits) were major confounders of most cross-sectional relationships between alcohol and serum lipids, blood pressure and body mass indices. The longitudinal relationships, however, were not confounded by changes in the other lifestyle behaviors. A significant nonlinear relationship was found for systolic blood pressure, in which drinkers of about 30 g/day had the lowest values. CONCLUSIONS: Moderate alcohol consumption and moderate long-term changes in alcohol consumption are positively related with the levels and changes in high-density lipoprotein cholesterol in healthy adult men and women. A moderate inverse association between alcohol and waist circumference may be expected. No relationships were found with triglycerides, blood pressure, body weight and the sum of the thickness of four skinfolds. Other lifestyle behaviors confound the cross-sectional, but not the longitudinal, relationships between alcohol consumption and serum lipids, blood pressure and body mass indices. Gender and type of beverage do not modify the relationships between alcohol consumption and these indices.

Adult↗

Mapping quantitative trait loci for longitudinal traits in line crosses.

Quantitative traits whose phenotypic values change over time are called longitudinal traits. Genetic analyses of longitudinal traits can be conducted using any of the following approaches: (1) treating the phenotypic values at different time points as repeated measurements of the same trait and analyzing the trait under the repeated measurements framework, (2) treating the phenotypes measured from different time points as different traits and analyzing the traits jointly on the basis of the theory of multivariate analysis, and (3) fitting a growth curve to the phenotypic values across time points and analyzing the fitted parameters of the growth trajectory under the theory of multivariate analysis. The third approach has been used in QTL mapping for longitudinal traits by fitting the data to a logistic growth trajectory. This approach applies only to the particular S-shaped growth process. In practice, a longitudinal trait may show a trajectory of any shape. We demonstrate that one can describe a longitudinal trait with orthogonal polynomials, which are sufficiently general for fitting any shaped curve. We develop a mixed-model methodology for QTL mapping of longitudinal traits and a maximum-likelihood method for parameter estimation and statistical tests. The expectation-maximization (EM) algorithm is applied to search for the maximum-likelihood estimates of parameters. The method is verified with simulated data and demonstrated with experimental data from a pseudobackcross family of Populus (poplar) trees.

Chromosome Mapping↗

Physiological comparison of the longitudinal and circular muscles of the pregnant rat uterus.

A comparative investigation of the longitudinal and circular muscles in the pregnant rat uterus (10-15 days) was made by means of electrical and mechanical recordings. The response of the circular muscle strip was characterized in the following respects: application of stretch caused acceleration of spontaneous activity that was greater in extent than in the longitudinal muscle strip; tetanic contraction was not produced by repetitive stimuli in the range of 0.1-5 Hz; slow potential was dominant in the circular muscle cells. The longitudinal contraction of the uterine segment occurred in synchronization with the change in the intraluminal pressure. Either the longitudinal stretch or the increase in the intraluminal volume caused the acceleration of synchronized activity. Stimulation of the longitudinal muscle caused membrane response in the circular muscle cells and vice versa, suggesting electrical interference between longitudinal and circular muscle cells.

Animals↗

Electrical and mechanical properties of longitudinal and circular muscles of the guinea-pig ileum.

The membrane potential of the electrically quiescent circular muscle fibre is higher than that of the spontaneously active longitudinal muscle fibre. The length constant of circular muscle fibres is longer than that of the longitudinal muscle. The electrical activity of the longitudinal muscle membrane is enhanced by caffeine and PGE1 is suppressed for the circular muscle. Isotonic K Krebssolution generates a large tonic response of the contracture of longitudinal muscle tissue, but in circular muscle it is small. Following an inward current pulse, a large rebound contraction of the circular muscle was generated during K-INDUCED CONTRACTURE BUT IT WAS SMALL IN THE LONGITUDINAL MUSCLE TISSUE. Caffeine suppressed the K-induced contracture of both tissues but enhanced the rebound contraction of the circular muscel. Verapamil and lanthanum suppressed the mechanical responses of both muscle tissues but rebound contraction evoked in isotonic K Krebs solution was of longer duration in circular muscle tissue than in longitudinal muscle tissues. It is postulated that both muscle tissues possess different electrical and mechanical properties, and that these differences are not caused by nervous activity.

Animals↗

The differences in contractile response to AC field stimulation between longitudinal and circular muscles of guinea pig stomach.

Contractile response to AC field stimulation was compared between the longitudinal and circular muscles of the guinea pig stomach under various stimulating conditions. The longitudinal muscle responded with considerable tension at any frequency between 20 and 2,000 Hz. The circular muscle showed a peak response around 200 Hz with rapidly decreasing response to the higher frequencies of less than 800 Hz. Experiments in the presence of tetrodotoxin and atropine revealed that the circular muscle was scarcely stimulated directly (without nerve excitation) by the AC, while the longitudinal muscle was stimulated directly at frequencies higher than 400 Hz, as well as being stimulated indirectly at frequencies lower than 200 Hz. The field strength necessary to generate one-half maximum tension was higher in the circular muscle (2.8 V/cm) than in the longitudinal muscle (1.5 V/cm at 200 Hz), although when a frequency lower or higher than 200 Hz was applied, the strength-tension curve shifted to the left or right, respectively. The contractile responses of the two muscles were graded with respect to filed duration up to maximum tension. The maximum tension and the highest rate of tension development were given at the stimulating condition of 200 Hz, 5 V/cm, for 5 sec in both types of muscles. The maximum tension generated per unit cross-sectional area of the longitudinal muscle was 19.2 g/mm2 and that of the circular muscle was 32.5 g/mm2. The maximum rates of tension development of the longitudinal and circular muscles wer 9.1 and 12.1 g/(mm2 . sec), respectively.

Animals↗

Role of netrin UNC-6 in patterning the longitudinal nerves of Caenorhabditis elegans.

The nervous system of Caenorhabditis elegans comprises circumferential and longitudinal axon tracts. Netrin UNC-6 is required for the guidance of circumferential axon migrations and is expressed by ventral neuroglia and neurons in temporally and spatially regulated patterns. Migrating axons mediate the UNC-6 signal through the UNC-5 and UNC-40 receptors. It is thought that UNC-6 is secreted and becomes associated with basement membranes and cell surfaces to form gradients that direct circumferentially migrating axons toward or away from the ventral UNC-6 sources. Little is known about the effects of UNC-6 on longitudinally migrating axons. In unc-6, unc-5, and unc-40 null mutants, some longitudinal nerves are dorsally or ventrally misdirected. Furthermore, the organization of axons are disrupted within nerves. We show that cells ectopically expressing UNC-6 can redirect the migrations of some neighboring longitudinal axons, suggesting that the gradients postulated to direct circumferential migration also help specify the dorsoventral positions of these longitudinal nerves. We also manipulated the temporal and spatial expression pattern of UNC-6 by two different means. First, we removed the PVT midline neuron which expresses UNC-6 for a short time during axon outgrowths. Second, we expressed UNC-6 uniformly in the nervous system throughout development. The results suggest that changing UNC-6 expression patterns modify the distribution of the cue by providing new localized sources. This new guidance information is critical for organizing the axons of longitudinal nerves.

Animals↗