Biomedical subjects

K S Murthy

Publications and source records attributed to K S Murthy.

At least 73 records · Page 4Linked to original sources

PubMed1993

Characterization of distinct receptors for the peptidyl leukotrienes LTC4 and LTD4/LTE4 coupled to the same signaling pathway in isolated gastric muscle cells.

Receptors for the peptidyl leukotrienes, (LT)C4, LTD4 and LTE4, and the signaling pathways to which they are coupled were characterized in isolated guinea pig gastric muscle cells. The three LTs were equipotent contractile agonists (EC50 values = 0.10-0.12 nM), but they elicited their responses by interacting with distinct receptors. The contractile responses to LTD4 and LTE4, but not LTC4, were inhibited by the LTD4 antagonist, SKF 104353 [2-(S)-hydroxy-3-(R)-[(2-carboxyethyl)thiol]-3-[2-(8- phenyloctyl)phenyl]-propanoic acid]. Similar Ki estimates for SKF 104353 suggested interaction of LTD4 and LTE4 with a common receptor. Decisive evidence for distinct LTC4 and LTD4/LTE4 receptors was obtained by applying a receptor protection technique. Cells in which LTC4 was used as a receptor protective agent while other receptors were inactivated by N-ethylmaleimide retained their responses to LTC4 only. Cells in which LTD4, LTE4 or SKF 104353 were used as a receptor protective agent retained their responses to LTD4 and LTE4 only. Both LTC4 and LTD4/LTE4 receptors were coupled to Pl hydrolysis: all three LTs stimulated similar increases in inositol 1,4,5-trisphosphate (IP3) levels (3.9-4.3 pmol/10(6) cells), protein kinase C activity (85-94 pmol/mg/min) and cytosolic-free Ca++ ([Ca++]i) (278-306 nM). Contractile responses were abolished: 1) when Pl hydrolysis was inhibited by neomycin and 2) when Ca++ stores were depleted by pretreatment of muscle cells with caffeine in Ca(++)-free medium, but not when muscle cells were incubated in Ca(++)-free medium or with Ca++ channel blockers, suggesting that contraction and [Ca++]i were mediated by IP3-dependent Ca++ release.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Synthesis and anticonvulsant activity of 1,3-dihydro-5-phenyl-2H-pyrido[3,4-e]-1,4-diazepin-2-ones.

1,3-Dihydro-5-phenyl-2H-pyrido[3,4-e]-1,4-diazepin-2-ones (6-21), in which the chlorophenyl ring of 7-chloro-1,4-benzodiazepin-2-ones is replaced by a pyridyl ring, were synthesized and evaluated as anticonvulsants using subcutaneous pentylenetetrazole (scPTZ) and maximal electroshock (MES) induced seizure screening tests. Structure-activity correlations indicated that a halo substituent at the 2-position of a 5-phenyl moiety enhanced scPTZ, but decreased MES, activity; the N1-substituent was a determinant of activity where the relative potency order was Me > CH2CH2NEt2 > cyclopropylmethyl; and that a 3-Me or 3-OH substituent generally decreased activity. This 1,3-dihydro-5-phenyl-2H-pyrido[3,4-e]-1,4-diazepin-2-one class of compounds had moderate affinity for the benzodoazepine receptor relative to clonazepam. In the mouse Phase II scPTZ screen all compounds tested were less active than clonazepam but more active than valproic acid, and in the MES screen all compounds tested were less active than phenytoin but more active than either clonazepam or valproic acid.

Animals↗

PubMed1992

Stimulation of nitric oxide from muscle cells by VIP: prejunctional enhancement of VIP release.

The source of nitric oxide (NO) and its role in neurally induced relaxation was examined in smooth muscle of the stomach and tenia coli. Field stimulation of gastric muscle strips was accompanied by frequency-dependent relaxation, vasoactive intestinal peptide (VIP) release, and NO production: the NO synthase inhibitor, NG-nitro-L-arginine (L-NNA) completely inhibited NO production and partly inhibited VIP release (52-54%) and relaxation (58-88%); inhibition of all three functions was reversed by L-arginine but not by D-arginine. In isolated gastric muscle cells, VIP caused relaxation and stimulated NO production: L-NNA completely inhibited NO production and partly inhibited relaxation; the inhibition was reversed by L-arginine but not by D-arginine. Abolition of NO production with only partial inhibition of relaxation implied that NO production from muscle cells induced by the action of VIP was partly responsible for relaxation. By contrast, field stimulation of tenia coli was accompanied by relaxation and VIP release but not by NO production. Neither VIP release nor relaxation was affected by L-NNA. In isolated muscle cells of tenia coli, VIP caused relaxation but did not stimulate NO production; relaxation in these cells was not affected by L-NNA. We conclude that 1) VIP is the primary relaxant transmitter in both gastric muscle and tenia coli, 2) the release of VIP in gastric muscle but not in tenia coli stimulates NO production from target muscle cells, and 3) NO amplifies the relaxant effect of VIP in muscle cells and acts presynaptically to enhance the release of VIP.

Animals↗

PubMed1992

Receptor-coupled G proteins mediate contraction and Ca++ mobilization in isolated intestinal muscle cells.

Guanosine 5'-O-(gamma-thio)triphosphate (GTP[S]), NaF and cholecystokinin-octapeptide (CCK-8) were used to examine the participation of G proteins in agonist-induced contraction of smooth muscle cells isolated separately from circular and longitudinal muscle layer of guinea pig intestine. All three agents stimulated inositol 1,4,5-triphosphate (InsP3) production and protein kinase C activity to the same extent in permeabilized (GTP[S] and CCK-8) and nonpermeabilized (NaF and CCK-8) muscle cells. InsP3 production was 9 to 13 times higher in circular muscle cells consistent with preferential hydrolysis of phosphatidylinositol 4,5-biphosphate in this cell type. InsP3 production and protein kinase C activation in permeabilized muscle cells were abolished by guanosine 5'-O-(beta-thio)diphosphate (10 microM). Maximal concentrations of GTP[S] (100 microM), CCK-8 (1 nM) and InsP3 (1 microM) elicited similar increases in [Ca++]i, net 45Ca++ efflux and contraction in permeabilized circular, but not longitudinal, muscle cells [( Ca++]i: 224 +/- 35 nM, 279 +/- 29 nM and 288 +/- 45 nM increase above basal level; 45Ca++ efflux: 35 +/- 2%, 34 +/- 3% and 37 +/- 3% decrease in cell Ca++ content; contraction: 26 +/- 2%, 24 +/- 2% and 25 +/- 2% decrease in cell length). The responses to GTP[S] and CCK-8 were abolished by guanosine 5'-O-(beta-thio)diphosphate (10 microM) and heparin (10 micrograms/ml), whereas the response to InsP3 was abolished by heparin only. Maximal concentrations of NaF and CCK-8 elicited similar increases in [Ca++]i and contraction in nonpermeabilized circular and longitudinal muscle cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Coexistence of contractile and relaxant 5-hydroxytryptamine receptors coupled to distinct signaling pathways in intestinal muscle cells: convergence of the pathways on Ca2+ mobilization.

Muscle cells were dispersed separately from circular and longitudinal muscle layers of guinea pig intestine, and 5-hydroxytryptamine (5-HT) receptors were characterized in naive cells and in cells in which one receptor type was preserved by selective receptor protection. In naive cells from both regions, 5-HT caused contraction and stimulated increases in cytosolic free calcium concentration ([Ca2+]i) (3-fold; p < 0.01) and cAMP levels (40-60%; p < 0.01) that were inhibited, respectively, by the 5-HT2 antagonist ketanserin and the 5-HT1p antagonist N-acetyl-5-hydroxytryptophyl 5-hydroxytryptophan amide (5-HTP-DP). In circular muscle cells, where agonist-induced increase in [Ca2+]i is mediated by Ca2+ release from inositol (1,4,5)trisphosphate-sensitive stores, 5-HT caused an increase in inositol (1,4,5)trisphosphate levels that was inhibited by ketanserin. In cells maximally contracted with a non-5-HT agonist (cholecystokinin octapeptide), 5-HT caused relaxation when the contractile effect mediated by 5-HT2 receptors was blocked with ketanserin; relaxation and the concomitant increase in cAMP were inhibited by 5-HTP-DP. The singular contributions of the Ca2+ and cAMP signaling pathways were identified in cells where only one receptor type was preserved. In cells with only 5-HT2 receptors, 5-HT caused contraction and an increase in [Ca2+]i but not in cAMP levels; contraction and the increase in [Ca2+]i were inhibited by ketanserin. Conversely, in cells with only 5-HT1p receptors, 5-HT caused relaxation and an increase in cAMP levels but not in [Ca2+]i; relaxation and the increase in cAMP levels were inhibited by 5-HTP-DP. The two signaling pathways were functionally linked, converging to regulate the level of [Ca2+]i. Thus, the increase in [Ca2+]i was augmented 1) when cAMP production was inhibited by 5-HTP-DP in naive cells or 2) when cAMP production was suppressed in cells where 5-HT1p receptors were inactivated and only 5-HT2 receptors were preserved. The results imply that the increase in cAMP levels mediated by 5-HT1p receptors acted to attenuate the increase in [Ca2+]i mediated by 5-HT2 receptors. We conclude that the response to 5-HT in muscle cells is a compound effect involving activation of two receptor types coupled to distinct signaling pathways that converge on [Ca2+]i as the determinant of mechanical activity.

5-Hydroxytryptophan↗

PubMed1991

Inhibition of muscle cell relaxation by somatostatin: tissue-specific, cAMP-dependent, pertussis toxin-sensitive.

The direct action of somatostatin on smooth muscle was examined in muscle cells isolated from the stomach and intestine of human and guinea pig. Somatostatin inhibited relaxation in gastric but not intestinal muscle cells of the two species, and its mechanism of action was explored in more detail in gastric muscle cells of the guinea pig. Somatostatin inhibited relaxation induced by vasoactive intestinal peptide (VIP, 83 +/- 7%, P less than 0.001) and isoproterenol (85 +/- 5%, P less than 0.001), as well as the concomitant increase in adenosine 3',5'-cyclic monophosphate (cAMP) production [81 +/- 25% inhibition with VIP (P less than 0.02) and 68 +/- 12% inhibition with isoproterenol (P less than 0.01)]. Inhibition of relaxation and cAMP production was abolished by pretreatment of the cells with pertussis toxin. Relaxation induced by the permeant derivative of cAMP, N6,2'-O-dibutyryladenosine 3',5'-cyclic monophosphate, by sodium nitroprusside, which acts by increasing levels of guanosine 3',5'-cyclic monophosphate, or by ATP, which acts by opening of K+ channels, was not affected by somatostatin. The fact that inhibition by somatostatin and its reversal by pertussis toxin was confined to agonists that stimulate an increase in the levels of cAMP implied that somatostatin acts by inhibiting the generation and not the action of cAMP. It is concluded that somatostatin receptors on gastric muscle cells mediate inhibition via a GTP-binding, pertussis-sensitive regulatory protein, Gi, coupled to adenylate cyclase.

Adenosine Triphosphate↗

PubMed1991

InsP3-dependent Ca2+ mobilization in circular but not longitudinal muscle cells of intestine.

The presence and functional coupling of inositol 1,4,5-trisphosphate (InsP3) receptors was examined in permeabilized muscle cells and microsomes isolated separately from the circular and longitudinal muscle layers of guinea pig intestine. Specific binding of [3H]InsP3 occurred only in circular muscle cells and microsomes; binding to longitudinal muscle cells or microsomes was minimal or absent. Binding to circular muscle cell microsomes was rapid (steady state in 2 min), saturable, reversible, and temperature independent, and was inhibited in a concentration-dependent manner by unlabeled InsP3 (IC50 10 nM) and by the InsP3 receptor antagonist heparin (EC50 4 micrograms/ml); inhibition by InsP4 and InsP2 was minimal. Consistent with the preferential location of InsP3 receptors, InsP3 elicited concentration-dependent contraction (EC50 3 nM), 45Ca2+ efflux (EC50 55 nM), and increase in [Ca2+]i in circular muscle cells and 45Ca2+ efflux in microsomes; all these events were blocked by heparin (10 micrograms/ml). Although ATP-dependent Ca2+ stores were present in longitudinal muscle cells and microsomes, they were not sensitive to 1 microM InsP3, which was maximally effective in circular muscle cells; 100 microM InsP3 elicited partial Ca2+ release (30-50%) and contraction (47%) that could only be blocked by high concentrations of heparin (100 micrograms/ml). We conclude that specific, high-affinity, heparin-sensitive InsP3 receptors capable of mobilizing intracellular Ca2+ are present predominantly in circular muscle cells of the intestine.

Animals↗

PubMed1991

Phosphoinositide metabolism in intestinal smooth muscle: preferential production of Ins(1,4,5)P3 in circular muscle cells.

The pattern of inositol phospholipid metabolism in response to stimulation by contractile agonists was examined in muscle cells isolated separately from circular and longitudinal muscle layers of guinea pig intestine. Addition of cholecystokinin octapeptide (CCK-8) to circular muscle cells caused a prompt decrease in phosphatidylinositol 4,5-bisphosphate (PtdInsP2) (50 +/- 6%) and PtdInsP (38 +/- 9%), which reached a nadir in 15 s. Addition of CCK-8 to longitudinal muscle cells caused a decrease in PtdInsP only (42 +/- 6%); PtdInsP2 levels, which were three times lower in this cell type, did not change throughout the period of stimulation. Hydrolysis of PtdInsP2 in circular muscle cells was accompanied by a concentration-dependent increase in inositol 1,4,5-trisphosphate [Ins(1,4,5)P3]; the maximal increase was 10 to 16 times greater in circular muscle cells as measured by radioreceptor assay and by ion-exchange chromatography. The small amounts of InsP3 produced in longitudinal muscle cells did not result from more rapid degradation, since the rates of disappearance of exogenous Ins(1,4,5)P3 in both cell types were similar. Within 5 s after addition of CCK-8, InsP3 comprised 73 +/- 5% of total inositol phosphates produced in circular muscle cells and 2.0 +/- 0.2% in longitudinal muscle cells. These divergent patterns indicate that inositol phospholipid metabolism is channeled toward generation of InsP3 in circular muscle cells only; the metabolic pattern in these cells parallels the selective presence of high-affinity InsP3 receptors and the pattern of intracellular Ca2+ mobilization.

Animals↗

PubMed1991

Surgical treatment of total anomalous pulmonary venous connection.

Fourteen infants ranging in age from 18 days to 10 months (median age = 4 months) underwent surgical repair of total anomalous pulmonary venous connection (TAPVC) between September, 1988 and December, 1989. The anomalous drainage was supracardiac in nine, cardiac in two, infracardiac in one and mixed in one. One patient had a complex type of TAPVC. There were two hospital deaths, one a critically ill three week old infant with obstructed infracardiac TAPVC and the other with complex TAPVC. There was no late death. All twelve survivors are in NYHA functional Class 1. Postoperative echocardiography revealed unobstructed pulmonary blood flow in all of them. Surgical correction of TAPVC in infancy has been performed with gratifying results. A high index of suspicion, early diagnosis, prompt referral and an aggressive surgical approach are essential for success in this otherwise lethal condition.

Cardiac Surgical Procedures↗

PubMed1990

Surgical treatment of major intracardiac lesions associated with discordant atrioventricular connexion.

Thirteen patients with a discordant atrioventricular connexion underwent repair of major associated intracardiac defects. Of the patients, 10 had a discordant ventriculoarterial connexion while 3 had double outlet from the morphologically right ventricle. A ventricular septal defect was the most frequently encountered lesion, present alone or in combination with other lesions in all patients. The other major lesions were pulmonary stenosis in 8, Ebstein's malformation of the left atrioventricular valve in 2, and calcific aortic valve disease in one. The operations performed were closure of the ventricular septal defect in 4 patients, closure of the ventricular septal defect with pulmonary valvotomy in 3 patients (one of whom subsequently underwent replacement of the left atrioventricular valve). Modified Fontan's procedure was performed in 6 patients, one of whom also had replacement of the aortic valve. There was no operative death, although there was one early death on the 40th postoperative day due to septicemia. There has been no late death after an average follow-up of 1.2 years. There was one case of surgically induced complete heart block. All other patients are in normal sinus rhythm in New York Heart Association functional class I or II. Elective repair of major intracardiac anomalies in association with a discordant atrioventricular connexion can now be accomplished safely. The modified Fontan's procedure is a viable alternative in certain cases to the placement of an external valved conduit for relief of pulmonary outflow tract obstruction.

Adolescent↗

PubMed1989

Effect of insulin on ATP-citrate lyase phosphorylation: regulation of peptide A and peptide B phosphorylations.

Insulin decreases multifunctional protein kinase (MFPK) activity in rat adipose tissue [Ramakrishna, S., & Benjamin, W. B. (1988) J. Biol. Chem. 263, 12677-12681]. Insulin also decreases the phosphorylation of peptide B but increases the phosphorylation of peptide A of ATP-citrate lyase (ATP-CL). The mechanism for this increase in peptide A phosphorylation was studied with purified ATP-CL from control and insulin- and isoproterenol-treated fat pads by using MFPK and the catalytic subunit of cAMP-dependent protein kinase (A-kinase). ATP-CL purified from insulin-treated fat pads is a better substrate for phosphorylation by MFPK compared to controls. This result is consistent with the hypothesis that insulin action decreases peptide B phosphorylation. To determine if the degree of phosphorylation at peptide B affects the phosphorylation rate of peptide A by A-kinase, ATP-CL was prepared with determined phosphate contents of peptides A and B. ATP-CL with a low phosphate content at peptide B is a better substrate for phosphorylation at peptide A by A-kinase than is ATP-CL with a high phosphate content at peptide B. These results suggest that the insulin-induced increase in ATP-CL phosphorylation at peptide A is due to a decrease in peptide B phosphorylation. ATP-CL prepared from isoproterenol-treated fat pads is also a better substrate for phosphorylation at peptide B by MFPK than controls. This increase in phosphorylation at peptide B by MFPK is due to positive second-site regulation by the isoproterenol-induced increase in peptide A phosphorylation.

ATP Citrate (pro-S)-Lyase↗

PubMed1988

In vitro release characteristics of hard shell capsule products coated with aqueous- and organic-based enteric polymers.

In this article, an overview of the rationale for the use of enteric coated (EC) dosage forms is presented. The benefits and disadvantages inherent in the use of aqueous dispersions and organic solutions of the various polymers to generate these products are discussed. The comparative dissolution stability of a hard shell capsule product coated with enteric polymers applied as either aqueous dispersions, or as organic solutions, were assessed under accelerated conditions of storage. Polymethacrylic acid methacrylate copolymer, cellulose acetate phthalate (CAP) and polyvinyl acetate phthalate (PVAP), along with the corresponding commercially available aqueous dispersions, Eudragit L30D, Aquateric, and Coateric, were employed in these studies as enteric polymers. Diethyl phthalate (DEP) was used as the plasticizer and procainamide HCl 250 mg capsules served as the substrate. Storage of the coated capsules at 37 degrees C/80% RH and at 45 degrees C for 2 months revealed that, while the stability of Eudragit L30D coatings are comparable or superior to the corresponding organic-based coatings, Coateric films are markedly unstable when compared with PVAP coatings applied through the use of organic vehicles. After storage at 37 degrees C/80% RH, Aquateric-based capsules demonstrated stability comparable to CAP organic-based coatings only when a protective seal coat was present. The performance failures of the capsules that occur upon storage primarily result in a loss of gastric resistance. Scanning Electron Microscopy (SEM) and thermomechanical analysis (TMA) of the different coatings revealed differences in the film-forming properties of the polymer films and provide an explanation for the changes that occur during storage of the coated capsules.

Capsules↗

PubMed1987

Retinal toxicity of trace elements.

Acute toxicity of lead, nickel and cobalt on rabbit retina was studied. It was found that all these metals produced similar photoreceptor degenerative changes, but lead produced extensive degenerative changes at ganglion cell layer also. Electroretinographically nickel group showed statistically (by analysis of variance) significant prolongation of 'b' wave implicit time as seen in autosomal dominant retinitis pigmentosa.

Animals↗

PubMed1985

The origins and characteristics of cross-correlated activity between gamma-motoneurones in the cat.

Cross-correlation analysis of the naturally occurring discharges of gamma-motoneurones to gastrocnemius and soleus muscles has revealed a tendency towards synchronized firing in the decerebrated, spinal cat. The primary feature of the cross-correlation between two gamma-motoneurones is a symmetrical peak centred at time zero with reference to discharges at the level of the cell bodies in the ventral horn of the spinal cord. The peak has a half-width in the range 3-10 ms. Secondary features of the correlograms are frequently present, especially when the primary peak is large. They consist of dips to either side of the peak and are mirrored in the respective autocorrelation functions of the two contributory neurones. This suggests that they arise as a result of periodicity in firing patterns of the neurones. The degree of synchrony has been measured as the ratio (k') of the total counts contributing to the peak over the number expected by chance. The value of k' was found to be dependent upon the firing frequencies of the neurones. Plots of k' against the geometric mean frequency of discharge showed a falling curvilinear relation as frequency increased. There was a weak inverse relation between the width of the cross-correlation peak and firing frequency. These relations had to be acknowledged before any assessment of change in the degree of synchrony could be made. The correlation between discharges is absent or weak in the decerebrated cat with an intact spinal cord and in intact cats anaesthetized with pentobarbitone or chloralose. Anaesthetics administered to a spinal animal did not suppress synchrony. The synchrony between gamma-motoneurones is characteristic of the short-term synchrony (Sears & Stagg, 1976) which arises from activity in shared presynaptic axons. In a few instances a stronger, more-tightly coupled synchrony was observed. The cross-correlogram peak had a half-width of 0.5-1.0 ms and was superimposed upon the usual wider-based peak. We presume that this intense form of synchrony has a different origin. The properties of the short-term synchrony are discussed with respect to (a) the mechanism of supraspinal control, and (b) a plausible model of the membrane properties of gamma-motoneurones which could account for the dependency of k' on frequency of firing. Experiments to determine the afferent source of synchronous firing and its distribution are presented in the following paper (Ellaway & Murthy, 1985).

Anesthesia↗

PubMed1985

The source and distribution of short-term synchrony between gamma-motoneurones in the cat.

The naturally occurring background discharges of gamma-motoneurones to gastrocnemius and soleus in the decerebrated, spinal cat show a degree of short-term synchrony which is absent when the spinal cord is intact. The characteristics of this synchrony and the mechanism producing it have been examined in the preceeding paper (Ellaway & Murthy, 1985). Short-term synchrony in the background discharge is removed by cutting the ipsilateral dorsal root (S1 or L7) at the segment of origin of the gamma-efferents. It persists on cutting other ipsilateral or any contralateral dorsal roots between L6 and S3. The source is not the homonymous or synergist muscle group. Neither is the skin which lies around the insertion of gastrocnemius-soleus on the heel the afferent source of this synchrony. However, stimulation of the heel by light stroking or pressure raises the frequency of gamma-efferent discharge and increases the degree of synchrony. Such stimulation does not produce synchrony in the decerebrated cat with an intact spinal cord. Synchrony between gamma-motoneurones is as strong between different fascicles of a muscle (gastrocnemius medialis), or different heads (gastrocnemius medialis and lateralis), as it is within one fascicle of a muscle. The timing of the peak incidence of correlated discharges always indicated synchrony at the level of the spinal cord irrespective of differences in peripheral conduction time or the destination of the axons. Hamstring and pretibial flexors show a lower incidence or weaker degree of short-term synchrony between homonymous gamma-efferents compared with gastrocnemius. Short-term synchrony is either weak or absent between gamma-motoneurones to heteronymous muscles. gamma-Efferents from homologous muscles on either side of the cord lack synchrony of discharge. The results go some way to establishing the source and connectivity to the motoneurone pool of afferents capable of synchronizing the discharge of gamma-efferents.

Afferent Pathways↗

PubMed1984

Reflex effects from high threshold neck muscle afferents on hind limb extensor gamma motoneurones in the cat.

The supra-segmental control of hind limb gamma motoneurones from neck muscle receptors has been studied in decerebrated and in spinal cats. Stretch of individual dorsal neck muscles was not an adequate stimulus for evoking long spinal reflexes to gamma motoneurones of gastrocnemius-soleus (GS) muscles unless the stretch was maximal or excessive. Pressure applied to the neck muscles, or intramuscular injections of KCl solution (0.1 ml, 5%), did affect the discharge of GS gamma motoneurones. Excitation was more evident than inhibition. We conclude that the long spinal reflex effects originate from high threshold mechanoreceptors, or nociceptors, rather than muscle spindles.

Animals↗

PubMed1983

Action of dantrolene sodium on single motor units of cat muscle in vivo.

Dantrolene sodium, a skeletal muscle relaxant, was investigated for its action on single motor units of the peroneus tertius muscle in cats anaesthetized with pentobarbitone sodium. Motor axons were isolated in ventral root filaments and their muscle units were identified as either fast-fatiguable (FF), fast-resistant (FR), fast-intermediate (FI) or slow-resistant (S). Dantrolene sodium (2 mg/kg) was administered intravenously in a solution of 1,2-propanediol. Effects were observed on the twitches, unfused tetanic contractions and maximal tetanic tensions of 78 motor units in 5 experiments. Contractile tension was depressed whereas muscle action potentials appeared unaffected. Maximal tetani were less depressed than unfused tetani and twitches. The reduction of tension was more pronounced for fast (FF, FR and FI) than for slow units. After drug injection, the mean tensions developed at the end of a 3 s period of stimulation at 40/s were: 13.1%, 10.6% and 12.7% of pre-drug control for FF, FR and FI units, respectively, and 67.1% for S units. Upon prolonged stimulation at 40/s fast units depressed by Dantrolene sodium were able to potentiate back to their initial pre-drug tension.

Action Potentials↗

PubMed1983

Patterns of fusimotor innervation by gamma-efferents in cat peroneus tertius.

The pattern of gamma-efferent innervation of the muscle spindle was investigated in the peroneus tertius muscle of the cat. A number of spindle group Ia afferents were isolated and monitored during tetanic stimulation of isolated gamma-axons. The sample was dominated by efferents producing a static fusimotor effect on the afferent. An individual static axon normally projected to less than five but at times as many as seven muscle spindles. Each spindle normally received innervation from three to five static gamma-efferents but occasionally up to eight. The number of spindles innervated by a static gamma-axon was directly related to the efferent axonal conduction velocity. For each experiment, a probability distribution of the number of fusimotor effects was constructed from all available connections between the muscle spindles and static gamma-efferents considered in matrices of four afferents and four efferents. This distribution was then compared to a random binomial distribution. In each of the ten experiments, statistically significant differences (p less than 0.01) were noted between the experimental and random distributions. In order to interpret such deviations from the random distributions, similar analyses were performed on various combinations of afferents and efferents in simulated sets displaying grouping of effects. It was concluded that the observed differences between experimental and random distributions may be produced by a grouping of fusimotor innervation limited to a small set of spindles.

Afferent Pathways↗