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Adrenergic receptor polymorphisms associated with resting heart rate: the HyperGEN Study.

The association between polymorphisms in the beta1, beta2 and alpha2B adrenergic receptor (ADR) genes (ADRB1, ADRB2 and ADRA2B) and resting heart rate was examined in white and African-American participants of the HyperGEN Study. All analyses were adjusted for age, sex, body mass index, alcohol use, smoking status and daily exercise within strata of race, hypertension status and beta-blocker use. The Ser49Gly polymorphism of the beta1 ADR was associated with resting heart rate in hypertensive African-Americans and hypertensive whites taking beta-blockers, with carriers of the Gly allele having a higher mean resting heart rate by 2.7 and 4.4 beats per minute (bpm), respectively. The Arg389Gly polymorphism of the beta1 ADR was associated with lower heart rate in the normotensive African-American sample. A beta1 haplotype (Ser49Gly-Arg389Gly) was modestly associated with resting heart rate in the hypertensive African-Americans. The alpha2B C/A polymorphism was associated with heart rate in hypertensive whites, and both whites and African-Americans taking beta-blockers, with carriers of the A allele having a higher mean resting heart rate. In summary, each of the ADR gene polymorphisms was associated with heart rate in at least one stratum studied, but there was no consistent association from which one would infer a large genetic contribution to heart rate.

Adrenergic beta-Antagonists↗

Changes in Achilles tendon moment arm from rest to maximum isometric plantarflexion: in vivo observations in man.

1. The purpose of the present study was to examine the effect of a plantarflexor maximum voluntary contraction (MVC) on Achilles tendon moment arm length. 2. Sagittal magnetic resonance (MR) images of the right ankle were taken in six subjects both at rest and during a plantarflexor MVC in the supine position at a knee angle of 90 deg and at ankle angles of -30 deg (dorsiflexed direction), -15 deg, 0 deg (neutral ankle position), +15 deg (plantarflexed direction), +30 deg and +45 deg. A system of mechanical stops, support triangles and velcro straps was used to secure the subject in the above positions. Location of a moving centre of rotation was calculated for ankle rotations from -30 to 0 deg, -15 to +15 deg, 0 to +30 deg and +15 to +45 deg. All instant centres of rotation were calculated both at rest and during MVC. Achilles tendon moment arms were measured at ankle angles of -15, 0, +15 and +30 deg. 3. At any given ankle angle, Achilles tendon moment arm length during MVC increased by 1-1.5 cm (22-27 %, P < 0.01) compared with rest. This was attributed to a displacement of both Achilles tendon by 0.6-1.1 cm (P < 0.01) and all instant centres of rotation by about 0.3 cm (P < 0.05) away from their corresponding resting positions. 4. The findings of this study have important implications for estimating loads in the musculoskeletal system. Substantially unrealistic Achilles tendon forces and moments generated around the ankle joint during a plantarflexor MVC would be calculated using resting Achilles tendon moment arm measurements.

Achilles Tendon↗

Alternate cardiovascular baseline assessment techniques: vanilla or resting baseline.

The accurate evaluation of cardiovascular reactions to psychological challenge requires stable baselines against which change can be evaluated. When more than one challenge is employed, the recovery of this baseline becomes important in order to avoid carryover effects. Resting periods, even those of 20 min or more, do not guarantee baseline stability. We compared a 20-min resting condition and a new form of baseline condition in 48 college men using video tasks as the psychological challenges. The new form was a minimally demanding color detection task, termed the "vanilla" baseline condition. A 10-min version and a 20-min version of this condition were tested. Comparisons to 10-min resting baselines were made using our prior work and values from the literature. Vanilla baseline conditions were shown to be equal to or better than resting baseline conditions using criteria of between- and within-baseline stability, amplitude and significance of responsivity, and generalizability between sessions on separate days. Ten-minute resting baselines also showed acceptable stability, questioning the value of lengthy baselines. The good performance of the 10-min vanilla baseline in initial and replication samples supported its utility for estimating baselines for many purposes.

Adolescent↗

Is DDD pacing superior to VVI,R? A study on cardiac sympathetic nerve activity and myocardial oxygen consumption at rest and during exercise.

Rate responsive ventricular pacing (VVI,R) has been demonstrated to equal atrial synchronous ventricular pacing (DDD) with regard to hemodynamics and exercise tolerance. Whether the two modes are also comparable, with regard to cardiac metabolic effects, is not yet clear. We assessed central hemodynamics, cardiac sympathetic nerve activity (cardiac norepinephrine overflow), and myocardial oxygen consumption in 16 patients treated with rate responsive atrial synchronous ventricular pacemakers (DDD,R) due to high degree AV block. The study was performed at rest and during supine exercise at two workloads (30 +/- 12 and 68 +/- 24 watts, respectively) during VDD and rate matched VVI pacing (VVIm). Ventricular rates at rest and during both workloads were almost identical. Cardiac output at rest tended to be higher in the VDD mode, due to a slightly higher stroke volume. Central pressures including right atrial pressure and pulmonary capillary wedge pressure were similar in the pacing modes. The coronary sinus blood flow, the coronary sinus arteriovenous oxygen difference, and the myocardial oxygen consumption did not differ between the two pacing modes. Cardiac norepinephrine overflow was similar in the two pacing modes, at rest or during exercise. Thus, we found no significant differences between VDD and VVIm pacing with regard to central hemodynamics, cardiac sympathetic nerve activity (cardiac norepinephrine overflow), or myocardial oxygen consumption either at rest or during moderate exercise.

Aged↗

Atrial near-field and ventricular far-field analysis by automated signal processing at rest and during exercise.

INTRODUCTION: Sophisticated monitoring of atrial activity is a prerequisite for modern pacemaker therapy. Ideally, near-fields and ventricular far-fields ought to be distinguished by beat-to-beat template analysis of the atrial signal. A prerequisite is that atrial signals are stable under different conditions. METHODS AND RESULTS: A Matlab routine was developed to analyze atrial electrograms of 23 patients at least 3 months after implantation of a dual chamber pacemaker under several conditions including at rest, bipolar at rest, in an upright position, during treadmill exercise, and postexercise. A near-field and far-field template was created and amplitudes, widths, and slew rates were measured. In bipolar configuration, near-field amplitude at rest was 3.04 +/- 0.94 mV (unipolar)/3.36 +/- 1.0 mV (bipolar) versus 3.18 +/- 1.0 mV (bipolar) at peak exercise. Far-field amplitude at rest was 1.66 +/- 1.18 (unipolar)/0.47 +/- 0.27 mV (bipolar) and 0.41 +/- 0.21 mV (bipolar) at peak exercise (n.s. for bipolar measurements). No overall significant changes were observed for near- and far-field widths and slew rates during exercise. Shorter tip-ring distances of the atrial bipole, lead position, and the presence of sinus node disease did not have any impact on overall near- and far-field signal characteristics. Intraindividual differences between rest and peak exercise were moderate (range: near-field +0.15 to -0.54 mV; range: far-field +0.05 to -0.18 mV). CONCLUSIONS: Atrial near and far fields can be automatically classified and quantified by automated signal processing. Signals did not change during exercise or change of posture. This is a prerequisite for the implementation of beat-to-beat template analysis into pacemakers.

Aged↗

Leg citrate metabolism at rest and during exercise in relation to diet and substrate utilization in man.

Previously we have demonstrated a lower rate of carbohydrate utilization in skeletal muscle after a fat than after a carbohydrate rich diet both at rest and during exercise. To test the hypothesis of citrate as a regulator of glycolysis (1) arterial-femoral venous (a-fv) differences for oxygen, citrate, pyruvate and lactate and (2) muscle citrate and glucose-6-phosphate (G-6-P) were determined at rest and after 5 and 25 min of submaximal bicycle exercise. Citrate release and muscle citrate concentration were higher after fat than after carbohydrate diet at rest and 5 min exercise, but did not differ between diets at 25 min exercise. Lactate release and muscle lactate concentration were lower after fat diet at 5 and 25 min exercise. Pyruvate release at 5 min exercise was higher after fat diet. The G-6-P concentration was higher at rest, insignificantly higher after 5 min exercise and lower at 25 min exercise after the fat diet. The findings support the notion that at rest and 5 min exercise fat diet induced inhibition of glycolysis might be mediated through increased intramuscular citrate acting on phosphofructokinase. In addition, the greater pyruvate release at 5 min exercise after fat diet in spite of a smaller lactate release, indicates a decreased pyruvate dehydrogenase activity and/or NADH to NAD ratio after fat diet. The inhibition of glycolysis at 25 min exercise after fat diet on the other hand does not seem to be citrate mediated.

Adult↗

Splanchnic and renal vasoconstrictor and metabolic responses to neuropeptide Y in resting and exercising man.

The local clearance of neuropeptide Y (NPY) and whether NPY influences splanchnic and renal metabolism in man have not been investigated previously. The influence of NPY on splanchnic and renal blood flows at physiologically elevated levels has also not been investigated. The effects of a 40-min constant NPY infusion (3 pmol kg-1 min-1) at rest and during 130 min of exercise (50% of VO2max) were studied in six healthy subjects and compared with resting and exercising subjects receiving no NPY. Blood samples were drawn from arterial, hepatic and renal vein catheters for the determination of blood flows (indicators: cardiogreen and para-aminohippuric acid [PAH]), NPY, catecholamines, glucose, lactate and glycerol. NPY infusion was accompanied by: (1) significant fractional extraction of NPY-like immunoreactivity (NPY-Li) by splanchnic tissues at rest (58 +/- 5%) and during exercise (53 +/- 6%), while no arterial-venous differences could be detected across the kidney; (2) a reduction in splanchnic and renal blood flows of up to 18 and 13% respectively (P less than 0.01-0.001) at rest without any additional changes during exercise; and (3) metabolic changes as reflected in: (a) a more marked fall in arterial glucose during exercise compared to the reference group (P less than 0.05); (b) a 35% lower splanchnic glucose release (P less than 0.01) during exercise due to diminished glycogenolysis (P less than 0.01); and (c) a lower arterial lactate level (18% P less than 0.05) together with unchanged splanchnic lactate uptake during exercise, suggesting reduced lactate production by extrahepatic tissues. The disappearance of plasma NPY-Li after the infusions was biphasic with two similar half-lives at rest (4 and 39 min) and during exercise (3 and 43 min).

Adult↗

Mechanisms for hypothermia-induced increase in contractile force studied by mechanical restitution and post-rest contractions in guinea-pig papillary muscle.

Lowering myocardial temperature increases contractile force, presumably by increasing intracellular calcium content. To study the mechanisms behind this, we compared the effects of some known inotropic interventions with hypothermia on mechanical restitution and post-rest contractile force in isolated guinea-pig papillary muscles. In four groups (n = 6 per group), the effects of: (1) reducing the ability for Na/Ca exchange to extrude Ca2+ (a) by increasing [Na+]i with ouabain or (b) by increasing [Ca2+]o; and (2) activation of calcium channels with Bay-K 8644, were compared with lowering temperature from 37 to 27 degrees C. Normally (at 37 degrees C and 2 mM CaCl2), mechanical restitution could be described by a rapid recovery phase with a time constant between 180 and 220 ms, followed by a slowly decaying phase with a time constant between 5000 and 8000 ms and post-rest contractions (1-10 min rest) were markedly depressed compared to steady-state contractions. Steady-state developed force was markedly increased at 27 degrees C, after 1 microM ouabain, 6 mM CaCl2 or 0.1 microM Bay-K 8644. At 27 degrees C the rapid recovery phase of restitution was delayed while the slowly decaying phase was not affected. Ouabain and increased [Ca2+]o caused elevation of the slowly decaying phase of restitution and markedly attenuated the post-rest depression of developed force, which may be attributed to a reduced diastolic extrusion of Ca2+ via the Na/Ca exchanger. Hypothermia and Bay-K 8644 on the other hand, augmented this post-rest depression. Hence, this study suggests that increased Ca2+ influx due to delayed inactivation of calcium channels may account for the increased developed force during hypothermia rather than reduced diastolic extrusion of Ca2+ via the Na/Ca exchanger.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Resting and dobutamine stress echocardiographic factors associated with the development of occult dilated cardiomyopathy in healthy Doberman pinscher dogs.

In 29 healthy Doberman Pinschers, echocardiographic parameters evaluating systolic and diastolic function were examined prospectively at rest and during dobutamine constant rate infusion (5 micrograms/kg/minute) to determine if any parameters were associated with the development of occult dilated cardiomyopathy (DCM). A resting echocardiogram was repeated 1 year later to determine which dogs had met our criteria for occult DCM. Six dogs developed occult DCM during the follow-up period. Univariate logistic regression analysis showed that at rest, an increased left ventricular internal dimension in systole (LVID-S) (P = .02), preejection period (PEP) (P = .03), ratio of PEP to left ventricular ejection time (P = .02), and isovolumic relaxation time (P = .02) were significantly associated with the development of occult DCM. During dobutamine stress echocardiography (DSE), high LVID-S (P = .02) and systolic wall stress index (P = .04) and reduced fractional shortening (P = .02) and ratio of peak early to late diastolic mitral filling velocity (E/A) (P = .05) were associated with the development of occult DCM. Multiple logistic regression showed that LVID-S (P = .002) and E/A (P = .002) measured during dobutamine infusion also were associated with the development of occult DCM. Reclassification based on the DSE data was not significantly different than reclassification based on the resting echocardiographic data. Resting echocardiography and DSE have the potential to be clinically applicable screening tests for very early systolic and diastolic dysfunction in Doberman Pinschers, heralding the onset of occult DCM as it is currently defined.

Animals↗

Where in the muscle spindle is the resting discharge generated?

This is a report of experiments on muscle spindles of the soleus muscle of the anaesthetized cat. Following a step shortening of the muscle, muscle spindles fall silent. At suitable muscle lengths their discharge may restart several seconds later to gradually recover a maintained rate of discharge. These experiments examine the question of where within the spindle the resumption of a resting discharge may originate. It was found that stimulation of some static fusimotor fibres immediately after the shortening led to early recovery of the resting discharge. Stimulation of dynamic and other static gamma motoneurones had much less effect. Since the dynamic gamma axons innervate almost exclusively the bag1 intrafusal fibre, contraction of this fibre appears to have little influence on the mechanisms responsible for restarting the resting discharge. Bag2 and chain fibres do seem to be involved. For primary endings, the bag2 fibre contraction was especially effective since static axons, which did not evoke 'driving' of the afferent response, and which are thought to predominantly innervate bag2 fibres, did restart the resting discharge. For secondary endings, stimulation of nearly all gamma axons led to an early restart of the resting discharge suggesting that here the nuclear chain fibres were responsible.

Animals↗

Transport and electrical phenomena in resting and secreting piglet gastric mucosa.

1. Gastric mucosae were isolated from piglets (0-5 days old) and mounted in a chamber where electrical properties and secretory function could be measured. Unlike many previously reported mammalian in vitro preparations, pig gastric mucosae were stable and physiologically responsive for many hours after isolation. 2. With similar Ringer solutions bathing both surfaces, the isolated piglet gastric mucosa maintained a p.d. with the mucosal surface 30-35 mV negative with respect to the serosal surface. Limitation of access of Na+ from the mucosal bathing solution to the tissue (e.g. replacement of Na+ on mucosal side with choline or treatment with 10- minus 5 M amiloride) produced a decrease in p.d. and increase in mucosal resistance consistent with an hypothesis of Na+ transport from mucosa to serosa. 3. Isotopic flux measurements (36Cl and 24Na) and net H+ secretory rate were performed during open and short-circuit conditions, while the tissue was at rest and after stimulation of HCl secretion by 6 times 10- minus 5 M histamine. Up to 90% of the respective short-circuit current for resting or secreting mucosae was accounted for as the algebraic sum of Cl minus, H+ or Na+ fluxes. 4. The net transport of Na+ which occurred from mucosa to serosa during rest (ca. 4-7 muequiv/cm2.hr) was somewhat reduced during HCl secretion (ca. 2-7 muequiv/cm2.hr). This active transport of Na+ was more resistant to anaerobiosis than was H+ or Cl minus transport. 5. An active transport component of Cl minus from serosa to mucosa was clearly demonstrable in the non-secreting preparations (ca. 3-9 muequiv/cm2.hr). Active Cl minus transport was stimulated three- to fourfold after H+ secretion was stimulated by histamine. Anaerobiosis promptly reduced Cl minus and H+ transport. An exchange diffusion component was demonstrated for Cl minus which appeared to be prominent during H+ secretory activity and was considerably diminished in resting mucosae. 6. Large changes in mucosal resistance were associated with conditions of rest, histamine stimulation and anaerobic conditions; mean values were 113, 74 and 197 omega.cm2, respectively. Electrical conductance of the isolated gastric mucosa was due primarily to partial ionic conductance of Cl minus (60-65%) and Na+ (10-15%). The partial conductance of H+ was extremely low. The observed increase in tissue conductance associated with H+ secretory activity and the changes in the long-time constant p.d. transient to a current pulse are discussed in terms of the relative contribution of the serosal and mucosal plasma membrane surfaces.

Anaerobiosis↗

Ionic basis of the resting potential of submucosal arterioles in the ileum of the guinea-pig.

1. The changes in the resting membrane potential of arterioles produced by rapid and brief changes in external ionic concentrations were measured. 2. The resting membrane potential was insensitive to changes in the external concentrations of both sodium and chloride ions but sensitive to changes in the external concentration of potassium ions. 3. Increasing the external concentrations of potassium ions produced depolarizations that were well described by the Nernst equation. 4. Decreased external concentrations of potassium ions produced membrane depolarizations which appeared to result not from inhibition of an electrogenic sodium pump but rather from a change in the resting conductance of the arteriolar membrane to potassium ions. 5. Ouabain caused both membrane depolarization and an increase in membrane resistance. 6. It is suggested that at rest, arteriolar smooth muscle is permeant predominantly to potassium ions, with only small contributions from chloride and sodium ions. No evidence was obtained which would support the idea that an appreciable proportion of the resting membrane potential depended upon current flow from an electrogenic sodium pump.

Animals↗

Release of adenosine, inosine and hypoxanthine from rabbit non-myelinated nerve fibres at rest and during activity.

The composition of the efflux from desheathed rabbit vagus nerve, loaded with radioactivity by incubation in [3H]adenosine, was studied at rest and during electrical activity and after application of inhibitors of ecto-enzymes and modifications of intermediary metabolism. In addition, the degradation of externally applied ATP and adenosine was examined. [3H]ATP applied to the incubation medium was degraded to ADP, AMP, adenosine and inosine. The hydrolysis to nucleosides was inhibited by alpha, beta-methylene ADP; the appearance of AMP and nucleosides was slowed by beta, gamma-methylene ATP. Deamination of [3H]adenosine was blocked by 2-deoxycoformycin. The effluent from resting and stimulated preparations showed the presence of large amounts of inosine and hypoxanthine, smaller amounts of adenosine and adenine and traces of nucleotides. The composition of the effluent was not significantly altered by addition of alpha, beta-methylene ADP; beta, gamma-methylene ATP or 2-deoxycoformycin. Application of glucose-free solutions caused a large release of adenosine instead of inosine and hypoxanthine and a small increase in resting and stimulated efflux of 3H. Addition of 2-deoxyglucose produced a large increase in resting efflux and increased liberation of adenosine. Cyanide, 2,4-dinitrophenol, arsenate or salicylate increased the resting efflux of adenosine, inosine and hypoxanthine, and the effect of activity. It is concluded that electrical activity leads to release of adenosine, inosine and hypoxanthine, in various proportions depending on metabolic state, and that there is practically no liberation of nucleotides from nerve axons.

Action Potentials↗

Changes in tetanic and resting [Ca2+]i during fatigue and recovery of single muscle fibres from Xenopus laevis.

1. Single muscle fibres were dissected from the toe muscles of Xenopus laevis and microinjected with Fura-2 to measure myoplasmic calcium concentration ([Ca2+]i). Injected fibres were illuminated at 340 and 380 nm and the ratio of the resulting fluorescence at 505 nm (the Fura-2 ratio) was taken as a measure of [Ca2+]i. Fibres were fatigued at 21 degrees C by repeated tetani until developed tension had fallen to 50% of control. 2. Tetanic tension declined monotonically during fatiguing stimulation, whereas the tetanic Fura-2 ratio first increased and then declined. At the 10th tetanus, tension was 87% of control whereas the Fura-2 ratio was 106% of control. At the end of fatiguing stimulation, where tension was around 50% of control, the tetanic Fura-2 ratio was reduced to 71%. The rate of decline of both tension and the Fura-2 ratio after a tetanus slowed during fatigue. During recovery, the tension and the tetanic Fura-2 ratio recovered in parallel. 3. The resting Fura-2 ratio increased throughout fatigue reaching 237% of control when tension had declined to 50%. There was a rapid phase of recovery, complete within 1 min, by which time the resting Fura-2 ratio was 198% of control. Subsequent recovery was slower and took 20-30 min to reach a stable level which was 121% of control. 4. The resting Fura-2 ratio towards the end of fatiguing stimulation was greater than the tetanic Fura-2 ratio in the early part of recovery although there was no detectable increase of resting tension during fatiguing stimulation. This observation suggests that the Ca2+ sensitivity of the contractile proteins was reduced at the end of fatiguing stimulation. 5. Plots of the tetanic tension against tetanic Fura-2 ratios throughout fatiguing stimulation and recovery also suggested that Ca2+ sensitivity was reduced during fatiguing stimulation when compared to recovery. 6. The increases in resting [Ca2+]i caused by raised [K+]o (from 2.5 to 10 mM) and/or by application of 15% CO2 were much less than those produced by fatiguing stimulation. Much of the elevated [Ca2+]i in fatigue could be reversed by application of dantrolene (25 microM). 7. The results suggest that both reduced tetanic [Ca2+]i and reduced Ca2+ sensitivity contribute to the decline of tension during fatigue.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

The effect of metabolic fuel on force production and resting inorganic phosphate levels in mouse skeletal muscle.

1. The effect of different metabolic fuels (glucose, pyruvate and lactate) and no exogenous metabolic fuel on force production was studied in isolated mouse soleus and extensor digitorum longus (EDL) muscles. Force was measured, at 25 degrees C, during isometric tetanic contractions and during contractions with isovelocity stretching and shortening. In parallel experiments, measurements were made of the resting phosphorus metabolite levels using 31P NMR. 2. In soleus muscles, the isometric tetanic force was potentiated with pyruvate (20 mM) as metabolic fuel, compared with glucose (11 mM), by 17.8 +/- 3.6% (mean +/- S.E.M., n = 6). The force was the same with no exogenous metabolic fuel, with glucose, or with lactate as metabolic fuel. The force exerted during shortening was also potentiated by pyruvate and by the same proportion as isometric force. However, during rapid stretching there was no force enhancement with pyruvate. The changes in the force seen with pyruvate are qualitatively similar to those produced when inorganic phosphate (Pi) is lowered in skinned rabbit psoas muscle fibres. 3. We tested whether the Pi content decreased in the presence of pyruvate by measuring resting Pi using 31P NMR spectroscopy. We found that, in soleus muscles, resting Pi was present with glucose and absent with pyruvate as metabolic fuel, and the effect was reversible. 4. EDL muscles produced the same isometric force whether the metabolic fuel was glucose, pyruvate, lactate or if no exogenous metabolic fuel was supplied. EDL muscles already had Pi levels below detectability at rest in glucose. There were no changes in the 31P NMR spectrum with pyruvate as metabolic fuel. 5. It appears therefore that the force potentiation in soleus muscles with pyruvate is due to a lowering of Pi. EDL muscles, which have a very low resting Pi in glucose, therefore have very little potential for force enhancement by this mechanism.

Animals↗

In vivo human gastrocnemius architecture with changing joint angle at rest and during graded isometric contraction.

1. Human gastrocnemius medialis architecture was analysed in vivo, by ultrasonography, as a function of joint angle at rest and during voluntary isometric contractions up to the maximum force (MCV). maximum force (MVC). 2. At rest, as ankle joint angle increased from 90 to 150 deg, pennation increased from 15.8 to 27.7 deg, fibre length decreased from 57.0 to 34.0 mm and the physiological cross-sectional area (PCSA) increased from 42.1 to 63.5 cm2. 3. From rest to MVC, at a fixed ankle joint angle of 110 deg, pennation angle increased from 15.5 to 33.6 deg and fibre length decreased from 50.8 to 32.9 mm, with no significant change in the distance between the aponeuroses. As a result of these changes the PCSA increased by 34.8%. 4. Measurements of pennation angle, fibre length and distance between the aponeuroses of the gastrocnemius medialis were also performed by ultrasound on a cadaver leg and found to be in good agreement with direct anatomical measurements. 5. It is concluded that human gastrocnemius medialis architecture is significantly affected both by changes of joint angle at rest and by isometric contraction intensity. The remarkable shortening observed during isometric contraction suggests that, at rest, the gastrocnemius muscle and tendon are considerably slack. The extrapolation of muscle architectural data obtained from cadavers to in vivo conditions should be made only for matching muscle lengths.

Adult↗

An estimate of the resting membrane resistance of frog olfactory receptor neurones.

The ability of a frog olfactory receptor neurone (ORN) to respond to odorous molecules depends on its resting membrane properties, including membrane resistance and potential. Quantification of these properties is difficult because of a shunt conductance at the membrane-pipette seal that is in parallel with the true membrane conductance. In physiological salines, the sum of these two conductances averaged 235 pS. We used ionic substitution and channel blockers to reduce the membrane conductance as much as possible. This yielded a lower limit for the membrane conductance of 158 pS. The upper limit of resting membrane resistance, then, is 6 GOmega. The membrane is permeable to K+ and, to a lesser extent, other cations. No resting Cl- conductance was detectable. Correcting measured zero-current potentials for distortion by the shunt suggests that the resting membrane potential is no more negative than -75 mV. The present results help to explain why frog ORNs are excitable at rest.

Animals↗

Human immunodeficiency virus type 1 can establish latent infection in resting CD4+ T cells in the absence of activating stimuli.

Resting CD4(+) T cells are the best-defined reservoir of latent human immunodeficiency virus type 1 (HIV-1) infection, but how the reservoir is formed is unclear. Understanding how the reservoir of latently infected cells forms is critical because it is a major barrier to curing HIV infection. The system described here may provide an in vitro model of latent HIV-1 infection in resting CD4(+) T cells. We demonstrated that HIV-1 integrates into the genomes of in vitro-inoculated resting CD4(+) T cells that have not received activating stimuli and have not entered cell cycle stage G(1b). A percentage of the resting CD4(+) T cells that contain integrated DNA produce virus upon stimulation, i.e., are latently infected. Our results show that latent HIV-1 infection occurs in unstimulated resting CD4(+) T cells and suggest a new route for HIV-1 reservoir formation.

Acquired Immunodeficiency Syndrome↗