Isometric Twitch Tension Research Articles

Effect of exercise on physiological age-related change at mouse neuromuscular junctions

To determine the effect of endurance exercise on physiological age-related change at the mouse neuromuscular junction (NMJ), synaptic function was studied for extensor digitorum longus (EDL) and soleus muscles of three C57BL/6J mouse groups, 1) young adult control (YC: 10 months), 2) old control (OC: 20 months), and 3) old mice which exercised (OE: 20 months) since young-adulthood. Electrophysiological properties were studied with intracellular recording techniques. Safety margin was studied by measuring indirect isometric twitch tension in different calcium concentrations. With sedentary aging, EDL and soleus quantal contents increased. Following aging combined with 10 months of exercise, the EDL quantal contents in OE and YC animals were similar. In contrast, soleus quantal content was greater in OE than in YC animals. Determined safety margins were OC>YC=OE for EDL, and OC=YC=OE for soleus. This is the first study to indicate that physiological age-related changes at NMJs of EDL and soleus muscles are affected differently by endurance exercise. Exercise prevented all physiological age-related changes in EDL NMJs but not in soleus NMJs, this suggests that EDL changes are associated with inactivity during aging, while soleus changes are “fundamental” age changes.

Effects of hypoxia, acidosis, and simulated ischemia on repriming of caffeine contracture in rat myocardium

This study was designed to examine the effects of hypoxia, acidosis, glucose-free medium and their combination on contraction and sarcoplasmic reticulum (SR) function in rat ventricular trabeculae. The isometric twitch tension was measured during superfusion with hypoxic (PO2 less than 30 mmHg), acidic (pH 6.80), glucose-free, or their combined ("ischemic") Tyrode's solution at 20 degrees C. The time needed to fully recover the contraction induced by 10 mM caffeine (repriming time) was measured to indirectly estimate the Ca2+ uptake of the SR. In "ischemia" and acidosis, the peak developed tension decreased progressively for the first 30 min (37.6 +/- 9.2% and 56.6 +/- 8.4% of control at 30 min, respectively), and then became steady. In hypoxic solution, the peak developed tension decreased moderately for the first 30 min (86.8 +/- 4.8% of control at 30 min), and thereafter remained steady. Developed tension did not change significantly during 60 min of superfusion with glucose-free solution. The repriming time of caffeine contraction was significantly delayed in both "ischemic" and hypoxic solutions, but was unchanged in acidic and glucose-free solutions. These results lead us to suggest that depressed SR function to accumulate Ca2+ may contribute to the decline in tension in ischemia and hypoxia, but that other mechanisms are important in the tension decline induced by acidosis.

Passive electrical properties, mechanical activity, and extracellular potassium in arterially perfused and ischemic rabbit ventricular muscle. Effects of calcium entry blockade or hypocalcemia.

The relation among passive electrical resistive properties, longitudinal conduction velocity, extracellular potassium concentration, [K+]o, and mechanical activity was investigated in the isolated rabbit papillary muscle during normal arterial perfusion and no-flow ischemia in the presence and absence of verapamil, or a reduced extracellular Ca2+ concentration [Ca2+]o. During normal arterial perfusion, verapamil (0.5 microM, free [Ca2+]o = 1.0 mM) and hypocalcemic blood perfusate (free [Ca2+]o = 0.4 mM) reduced the maximal isometric twitch tension by 48% and 78%, depolarized the resting membrane by +3 and +7 mV, decreased the extracellular longitudinal resistance (ro) by 15% and 26%, and increased conduction velocity by 4% and 6%, respectively. The changes in conduction velocity during these interventions were consistent with those predicted by linear cable theory (+3% and +9%) for the observed changes in ro. In contrast, verapamil shortened whereas a reduced [Ca2+]o lengthened action potential duration. Comparison of simultaneously measured longitudinal whole tissue resistance (rt), intracellular longitudinal resistance (ri), [K+]o, and resting tension during ischemia showed a close association between abrupt cell-to-cell electrical uncoupling, development of ischemic contracture, and the secondary rise of [K+]o, which all started to develop after approximately 15 minutes of ischemia. Electrical cell-to-cell uncoupling was completed within 15 minutes. In the presence of verapamil, the relation among the onset of electrical cell-to-cell uncoupling, secondary rise of [K+]o, and onset of ischemic contracture in ischemia was qualitatively the same as in its absence; however, these events were postponed by approximately 10 minutes, and the rates of contracture development and uncoupling were diminished. Conduction velocity decreased after 12 minutes of ischemia from 54 to 36 cm/sec in the absence of and from 61 to 46 cm/sec in the presence of verapamil. This slowing effect on impulse conduction could not be attributed to changes of electrical cell-to-cell coupling because at this time an increase in ri had not yet taken place. In the presence of a reduced [Ca2+]o, the resting tension and ri increased almost immediately after the onset of ischemia. Although the resting tension rose progressively throughout the course of ischemia, the ri showed a biphasic increase characterized by an early transient increase that reached a peak at 8 minutes (+87%) and a second, irreversible increase beginning at approximately 12 minutes. This final onset of electrical cell-to-cell uncoupling and the secondary rise of [K+]o were not different from the findings with a normal [Ca2+]o.(ABSTRACT TRUNCATED AT 400 WORDS)

Length‐dependence of isometric twitch tension potentiation and myosin phosphorylation in mouse skeletal muscle

The effect of changes in muscle length on post-tetanic isometric twitch tension potentiation and myosin P-light chain phosphorylation was studied at 23 degrees C in the mouse extensor digitorum longus muscle. The length-tension relationship was determined for the same muscles after a 30 min period of quiescence and between 30 s and 3 min after a 1.5 s tetanus at L0. Isometric twitch tension is increased at all muscle lengths after the tetanus; however, the fractional increase in twitch tension rises from 0.2 at L0 to a maximum of 0.3 at 1.2 L0. The fractional increase in twitch tension measured at any fixed muscle length is constant between 30 s and 3 min post-tetanus. P-light chain phosphorylation remains constant between 30 s and 3 min post-tetanus followed by a slow decline to basal values. Under fixed length conditions, there is linear relationship between the relative magnitude of the twitch tension and the extent of P-light chain phosphorylation. Net myosin phosphorylation measured after a 1.5 s tetanus at 1.23 L0 is 35% less than that obtained under the same conditions at L0. Thus, contraction-induced phosphorylation of P-light chain decreases with increased muscle length and post-tetanic potentiation at a constant level of P-light chain phosphorylation increases with increasing muscle length. These observations may be consistent with alterations in the sarcoplasmic Ca2+ ion transient as the muscle is lengthened.

The Effects of Short- and Long-Term Corticosteroid Treatment on Rat Diaphragm Contractility and Fatigue

Male Wistar rats received dexamethasone (1.5 mg/kg/day) hind-limb injections for 2.5 weeks (D—2.5 wk, N = 10) and 10 weeks (D—10 wks, N = 9). Controls were pair-fed and injected daily with saline solution. All groups had similar weights initially (186 ±2 g). Pneumonia was not a complication. Hemidiaphragm costal strips were bathed in modified Krebs (37°C) containing insulin and d-tubocurarine. At optimal length, isometric twitch (2ms, sq wave) and tetanic tensions (400 ms trains at 10, 20, 60, and 100 Hz), normalized for muscle strip csa (g/cm2), were measured at baseline BI, after 10 min of fatiguing stimulation (5 impulses at 5 Hz; 30 trains/min) and after 10 min of recovery.

Isometric twitch tension of lateral muscle in carp, Cyprinus carpio L., with sekoke disease

. Changes in blood properties and the chemical components, histology and isometric twitch tension of lateral muscle were studied in carp, Cyprinus carpio L., showing clinical signs of sekoke disease induced by a diet containing oxidized oil. When compared to normal fish, sekoke fish were found to have significantly lower mean blood pH, haematocrit, haemoglobin concentration and muscle water content. However, plasma lactate, lipoperoxide and total lipid concentrations were significantly higher in sekoke fish. It was found that in sekoke fish the maximum tension and the number of isometric twitches leading to complete fatigue of lateral muscle were greatly reduced. Histological studies confirmed that these reductions were related to the degree of structural damage within this tissue.

Eosinophils from hypereosinophilic patients damage endocardium of isolated feline heart muscle preparations.

Persistent eosinophilia in humans is often associated with endocardial damage to the heart, but a causal relation has not been established. We investigated the effect of eosinophils and eosinophil supernatants obtained from eight hypereosinophilic patients on the contractile performance and endocardial morphology of isolated, electrically stimulated cat papillary muscle preparations (n = 16). All these eosinophil suspensions contained high proportions of "hypodense" or "activated" cells. Eosinophils (5-15 x 10(6) ml organ bath) or eosinophil culture supernatants (prepared by overnight incubation at 37 degrees C) when added to papillary muscles produced acute changes in contractile behavior of these muscles identical to the previously reported effects of selective endocardial damage: a reduction in time to peak isometric twitch tension causing a reduction in peak isometric tension but with no significant reduction in rate of tension development or in maximum unloaded shortening velocity. All of these muscle preparations showed severely damaged endocardium at scanning electron microscopy. Addition of eosinophils from hypereosinophilic patients to muscles with selectively damaged endocardium (by previous transient [1-second] exposure to 1% Triton X-100) produced no further change in contractile performance. No significant change in contractile performance or endocardial morphology of papillary muscles (n = 16) was observed after addition of eosinophils (7.5-10 x 10(6] or neutrophils (8-15 x 10(6] from normal subjects or of cell-free culture medium. Thus, activated human eosinophils produce specific morphological and functional changes suggestive of specific damage to endocardium of isolated feline cardiac muscle.

Endocardium modulates myocardial inotropic response to 5-hydroxytryptamine.

The endocardium modulates contractile performance of subjacent myocardium in isolated heart muscle. We investigated the effects of 5-hydroxytryptamine (5-HT, 0.01-30 microM) on isolated cat papillary muscles with or without intact endocardium (+E or -E, respectively). Selective endocardial damage by 1-s immersion in 1% Triton X-100 caused reduction in half-isometric relaxation time (RT1/2) and isometric twitch tension (TT), but not maximum unloaded shortening velocity (Vmax). 5-HT caused reduction in RT1/2 in endocardium-intact but an increase in endocardium-damaged preparations (at 30 microM: -12.1 +/- 1.8%, +E; +5.2 +/- 1.5%, -E). Mean percent increases in TT were greater in endocardium-damaged muscles (at 30 microM: 37.3 +/- 8.6%, +E; 107.3 +/- 19.5%, -E). In the presence of ketanserin (1 microM), 5-HT reduced RT1/2 in endocardium-intact (at 30 microM: -11.9 +/- 1.3%) but not endocardium-damaged muscles (except slightly at 30 microM) and increased TT at 30 microM by 28.7 +/- 4.9% (+E) and 48.9 +/- 15.6% (-E). In the presence of propranolol (1 microM), 5-HT increased RT1/2 (+E and -E) while increasing TT by 23.3 +/- 7.8% (+E) and 43.5 +/- 2.5% (-E). Endocardium did not influence changes in Vmax. Ketanserin (1 microM), but not propranolol (1 microM), markedly diminished endocardial damage induced by 5-HT (greater than or equal to 10 microM). These results suggest a 5-HT-induced endocardium-mediated "inhibitory" effect (causing earlier isometric relaxation) that is not blocked by ketanserin.

Myosin light chain phosphorylation and tension potentiation in mouse skeletal muscle.

In intact mammalian fast-twitch skeletal muscle, a quantitative relationship exists between the phosphate content of myosin P-light chain (PLC) and the extent of isometric twitch tension potentiation. It has been proposed that PLC phosphorylation causes twitch potentiation in intact muscle by rendering the contractile element more sensitive to activation by Ca2+. If this hypothesis is correct, then an obligatory experimental outcome is that the slope of the "PLC phosphate vs. isometric tension potentiation (ITP)" relationship should increase when the amount of Ca2+ available to activate the contractile element is decreased. Intact mouse extensor digitorum longus muscles were studied in the absence and presence of sodium dantrolene, an agent that partially inhibits Ca2+ release from the sarcoplasmic reticulum (SR). Treatment of muscles with dantrolene produced a 73% reduction in isometric twitch tension and an approximately threefold increase in the slope of the PLC phosphate vs. ITP relationship. Under experimental conditions that produced fused, tetanic contractions equal to 0.52, 0.72, 0.94, and 1.0 force production, contraction-induced changes in PLC phosphate content were directly proportional to the extent of contractile element activation, whereas the extent of ITP was inversely proportional to the extent of contractile element activation. These data indicate that the slope of the PLC phosphate vs. ITP relationship varies inversely as a function of the amount of Ca2+ that is released from the SR to activate the contractile element during both twitch and fused, submaximal tetanic contractions. Furthermore, these findings support the hypothesis that ITP in intact skeletal muscle is due to a PLC phosphorylation-induced sensitization of the contractile element to activation by Ca2+.

Pathologic changes and contractile properties of the diaphragm in corticosteroid myopathy in hamsters: comparison to peripheral muscle.

Corticosteroids have been shown to produce a myopathy of peripheral skeletal muscle, characterized predominantly by Type II fiber atrophy. To determine if similar histologic and histochemical changes occur in the diaphragm and whether the in vitro contractile properties of this muscle are adversely affected by steroids, we studied two groups of hamsters. The experimental group received triamcinolone while a control group received saline, both given daily for 3 wk as i.m. injections. Soleus (Sol) and extensor digitorum longus (EDL) muscles and costal diaphragm muscle sections were stained for histologic (hematoxylin and eosin, modified Gomori trichrome) and histochemical (myosin ATPase, succinate dehydrogenase [SDH]) analysis. Muscle fiber proportions and cross-sectional areas (CSA) were measured from myosin ATPase sections. In vitro studies of isometric contractions were carried out on small strips of costal diaphragm, measuring maximal isometric twitch (Pt) and tetanus (Po) tensions, time to peak tension (TTP), half relaxation time (1/2 RT), force-frequency relationship, and fatigue characteristics (60 Hz tetani; duty cycle, 0.5). Triamcinolone treatment resulted in no change in muscle fiber proportions. There was no effect on Type I fiber CSA; however, there was Type IIa (Sol, EDL) and Type IIb (diaphragm, EDL) fiber atrophy in triamcinolone-treated animals. Pt and Po (normalized for weight) of diaphragm strips were not different. There was a prolongation in TTP and 1/2 RT, a left shift in the force-frequency curve, and a reduced fatiguability of triamcinolone-treated diaphragm (P less than 0.05). We conclude that a steroid myopathy could be explained by a loss of muscle mass (Type IIb fiber atrophy) rather than an intrinsic impairment in contractile function.(ABSTRACT TRUNCATED AT 250 WORDS)

Myocardial inotropic responses to aggregating platelets and modulation by the endocardium.

Ventricular mural thrombi complicate many cardiac diseases. The endocardial endothelium can modulate the mechanical performance of subjacent myocardium and mediate responses to certain physiopharmacologic agents. We studied the effects of aggregating platelets on the contractile performance of isolated cardiac muscle. The role of the endocardium was investigated by selectively damaging it by very brief (1 second) exposure to 1% Triton X-100 in some muscle preparations before experiments. Cat papillary muscles (n = 54) were attached to an electromagnetic length-tension transducer in organ baths containing Krebs-Ringer solution (1.25 mM Ca2+, 35 degrees C), and stimulated electrically at 0.2 Hz. Homologous washed platelets (final concentration 3 x 10(11)/l) aggregated spontaneously on addition to baths. Mechanical performance increased significantly more in muscles with damaged endocardium than in intact muscles (p less than 0.05); total peak isometric twitch tension increased by 31.8 +/- 7.8% (with damaged endocardium) and 11.8 +/- 2.6% (with intact endocardium), and peak isotonic twitch shortening increased by 36.7 +/- 7.8% (with damaged endocardium) and 9.6 +/- 2.0% (with intact endocardium). Increases in maximum velocity of unloaded shortening were similar in both muscle groups. Time to half isometric twitch tension decline decreased in intact muscles (3.6 +/- 1.0%) but increased in Triton-treated muscles (2.5 +/- 1.3%, p = 0.003 for difference between groups). The inotropic response to platelets in muscles with intact endocardium was unaltered by pretreatment of muscles with indomethacin (10 microM) or by stimulation of platelet aggregation with thrombin (0.1 unit/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Org.2766 stimulates collateral sprouting in the soleus muscle of the rat following partial denervation

The influence of melanocortins on the process of collateral sprouting has been investigated in rat soleus muscle. The soleus muscle was partially denervated by transecting and ligating the L5 mixed nerve. Collateral sprouting was assessed by means of isometric twitch tension measurements of soleus motor units that remained following L5 transection. The smaller the number of remaining soleus motor units, the larger the extent of collateral sprouting. Seven days following partial denervation, the index of sprouting (ratio between twitch tension of motor units in partly denervated muscles and in normal muscles) was significantly increased by treatment with the ACTH4-9 analog Org.2766 (1 microgram/48 hours). This increase appeared to be present also 28 days following partial denervation. The electrophysiological results were confirmed by histological investigations. The results provide evidence that Org.2766 increases the motor neuron collateral sprouting capacity of peripheral nerve. Org.2766 did not induce muscle fiber hypertrophy.

Length-tension relationship of striated muscle of cat external anal sphincter.

The active and passive length-tension curves of small strips of cat external anal sphincter (EAS) were examined in vitro. The striated muscle fibers were arranged perpendicular to the long axis of the longitudinal smooth muscle cells of the longitudinal layer of the anal canal. Histological examination indicated that the strips were comprised of striated muscle fibers oriented in the long axis of the strip. Electrical field stimulation elicited twitch and tetanus responses that were not altered by the administration of gallamine triethiodide (10(-6) to 10(-4) M), a neuromuscular blocking agent. At 37 degrees C the time from the onset of the twitch contraction to the development of peak force ranged from 30 to 37 ms, the time from peak force to one-half relaxation ranged from 20 to 25 ms. The maximum active twitch and tetanus tension (Po) averaged 0.23 and 0.90 kg/cm2, respectively. Active tension could be developed over a range of 0.6-1.4 optimum length (Lo). The passive length-tension curve showed that the muscle had significant passive tension at lengths below the Lo for tension development and a high passive tension at Lo (average of 44% of active isometric twitch tension, 12.2% of active isometric tetanus tension) and above Lo. We conclude that the passive length-tension curve for the EAS is stiffer than that of typical mammalian skeletal muscles. We suggest that this difference is related to the adaptation of the EAS to its sphincteric function as a component of a hollow organ.

Bioenergetic changes during contraction and recovery in diabetic rat skeletal muscle.

Phosphorus nuclear magnetic resonance (31P-NMR) spectroscopy was used to assess the effects of hypoinsulinemia on skeletal muscle during contraction in vivo. Five groups of rats were studied: age-matched (CONA) and weight-matched (CONW) nondiabetic controls; rats given streptozotocin 21 days before study (UD); diabetic rats treated with insulin for 21 days (ITD); and insulin-treated diabetic rats with insulin treatment withheld for 72 h before study (IWD). Both UD and IWD had similar alterations in plasma substrate concentrations and an impairment in the rate of glycogen resynthesis after the stimulation protocol compared with ITD, CONA, and CONW. Pyruvate oxidation was decreased by 30-40% in mitochondria isolated from gastrocnemius of the UD group, whereas no significant decrease was observed for mitochondria from the IWD (or ITD) group(s). In UD, maintenance of gastrocnemius muscle isometric twitch tension at 1 Hz required exaggerated decreases in phosphocreatine (PCr) concentration and pH; at 5 Hz, muscle performance declined significantly, and intracellular pH decreased to lower values than observed for the control groups; during recovery, no impairment of PCr resynthesis was observed. We conclude that in skeletal muscle of UD 1) at 1 Hz there is an increased reliance on glycolytic mechanisms of ATP resynthesis and 2) at 5 Hz force failure may occur because of the decreased rate of pyruvate utilization.

Functional regeneration in the hindlimb skeletal muscle of the mdx mouse.

The pattern of spontaneous skeletal muscle degeneration and clinical recovery hindlimb muscles of the mdx mutant mouse was examined for functional and metabolic confirmation of apparent structural regeneration. The contractile properties, histochemical staining and myosin light chain and parvalbumin contents of extensor digitorum longus (EDL) and soleus (Sol) muscles of mdx and age-matched control mice were studied at 3-4 and 32 weeks. Histochemical staining (myofibrillar ATPase and NADH-tetrazolium reductase) revealed no significant change in slow-twitch-oxidative (SO) or fast-twitch-oxidative-glycolytic (FOG) fibre type proportions in mdx Sol apart from the normal age-related increase in SO fibres. At 32 weeks mdx EDL, however, showed significantly smaller fast-twitch-glycolytic (FG) and larger FOG proportions than those in control EDL. These fibre type distributions were confirmed by differential staining with antibodies to myosin slow-twitch and fast-twitch heavy chain isozymes. Frequency distribution of cross-sectional area for each fibre type showed a wider than normal range of areas especially in FOG fibres of mdx Sol, and FG fibres of mdx EDL, supporting previous observations using autoradiography of myofibre regeneration. Isometric twitch and tetanic tensions in Sol were significantly less than in controls at 4 weeks, but by 32 weeks, values were not different from age-matched controls. In mdx EDL at 3 weeks, twitch and tetanus tensions were significantly less, and time-to-peak twitch tensions were significantly faster than in control EDL. By 32 weeks, mdx EDL twitch and tetanus tensions expressed relative to muscle weight continued to be significantly lower than in age-matched controls, despite normal absolute tensions. The maximum velocity of shortening in 32-week mdx EDL was significantly lower than in control EDL. Myosin light chain distribution in mdx Sol exhibited significantly less light chain 2-slow (LC2s) and more light chain 1b-slow(LC1bs) at 32 weeks than age-matched control Sol. Gels of EDL from 32-week-old mdx mice showed significantly less light chain 2-fast-phosphorylated (LC2f-P) and light chain 3-fast (LC3f) and significantly more light chain 1-fast (LC1f) and light chain 2-fast (LC2f), but normal parvalbumin content compared to age-matched controls. These observations suggest that mdx hindlimb muscles are differentially affected by the disease process as it occurs in murine models of dystrophy. However, the uniqueness of mdx Sol and to a lesser extent EDL is that they also undergo an important degree of functional regeneration which is able to compensate spontaneously for degenerative influences of genetic origin.(ABSTRACT TRUNCATED AT 400 WORDS)

Alterations in contractile properties of extensor digitorum longus muscle from [formula omitted] mice following denervation at 1 day of age

Changes in contractile properties of developing fast-twitch skeletal muscle of the C57 BL6J mouse were studied following neonatal denervation. A sciatic neurectomy was performed at 1 day of age and then denervated and control muscles were examined at 7, 14, and 21 days postdenervation. In addition, normal muscles were studied at 1 day of age. The denervated muscles exhibited prolongation of time-to-peak twitch tension and half-relaxation time, a slowing of the maximum velocity of shortening, and a marked increase in resistance to fatigue compared with controls. Isometric tetanus tension was reduced compared to the control muscle both in absolute terms and when expressed relative to body weight at all ages studied. The absolute isometric twitch tension was reduced at 7 and 14 days, but was reduced only at 21 days when expressed as a fraction of the muscle weight. Post-tetanic twitch potentiation failed to appear in the denervated muscle. It would appear that neonatal denervation results in an uncoupling of the developmental pattern of skeletal muscle.

The effect of intraoperative ischemia on the recovery of contractile function after free muscle transfer

Isometric contractile function was studied after recovery in free, vascularized muscle transfer subjected to graded periods of intraoperative ischemia. Fifteen dogs had orthotopic replantation of their left gracilis muscles, with intraoperative ischemia times grouped as 0 (n = 3), 1 to 2 (n = 3), 2 to 3 (n = 4), or 3 to 4 (n = 5) hours. After recovery (mean 61.8 weeks), isometric twitch and tetanic tension and fatigue measurements were made in the replants and in the contralateral, control gracilis. On the average, replants were found to produce significantly less twitch (0.32 +/- 0.13 versus 0.49 +/- 0.24 N/g) and 75 Hz tetanic tension (2.2 +/- 0.9 versus 3.4 +/- 0.5 N/g) than controls. However, in several individual replants, 100% of control maximal tetanic tension was observed. Intraoperative ischemia time of up to 4 hours was not correlated with functional return. It is concluded that (1) full recovery is possible after free muscle transfer; (2) intraoperative ischemia, if less than 4 hours long, is not the primary determinant of functional recovery; and (3) factors besides intraoperative ischemia must be operative in producing the variability in recovery seen in this setting.

Relationship between parvalbumin content and the speed of relaxation in chronically stimulated rabbit fast-twitch muscle.

The time courses of changes in parvalbumin (PA) content, isometric twitch tension, and half-relaxation time (1/2 RT) were studied in rabbit tibialis anterior muscle following chronic 10 Hz nerve stimulation of 1-21 days. Up to 5 days stimulation had no effect on PA content, but it induced a slight (10-15%) increase in the 1/2 RT. This change occurred together with the previously observed 50% decrease in Ca2+-uptake by the SR (Leberer et al. 1987). While prolonged stimulation produced no further decrease in the Ca2+-uptake by the SR, PA content declined after 5 days of stimulation. The reduction in PA content was accompanied by a progressive lengthening of the 1/2 RT. However, the increase in 1/2 RT was particularly pronounced after PA had fallen below 50% of its normal value. A 90% reduction in PA coincided with a 60% increase in the 1/2 RT. By this time the staircase phenomenon, normally observed in fast-twitch muscle, was completely abolished. Although the changes in PA content and 1/2 RT were not linearly related, these results suggest that PA plays an important role in the relaxation process of mammalian fast-twitch muscle.

Effects of damaging the endocardial surface on the mechanical performance of isolated cardiac muscle.

The mechanical properties of mammalian ventricular cardiac muscle have been studied in the presence and in the absence of an intact endocardial surface. Isotonic and isometric twitch contractions were obtained from papillary muscles of the right ventricle of cat at 29 degrees and 37 degrees C, at different extracellular calcium concentrations ([Ca2+]o), and at different initial muscle lengths. The endocardial surface was damaged by gentle abrasion of the muscle surface with a plastic blade or by brief immersion for 1 second with 1% Triton X-100. Although there was no evidence of damage to myocardial cells, damaging the endocardial surface resulted in an immediate and irreversible abbreviation of the twitch contractions with, except at the highest ([Ca2+]o, a decrease in peak isometric twitch tension. These changes induced 1) an asymmetrical shift of the tension-[Ca2+]o relation towards increasing [Ca2+]o but with no effect at the highest [Ca2+]o, and 2) a rightward and downward shift of the length-tension relation. Both shifts were significantly more pronounced at 37 degrees C than at 29 degrees C; they were not accompanied by significant changes in Vmax. The asymmetrical shift of the tension-[Ca2+]o relation suggests that the endocardium-mediated chain of events may be mediated by changes in the sensitivity of the contractile proteins to Ca2+. This hypothesis is also supported by the similar pattern of changes (i.e., modulation of the onset of early tension decline) induced by decreasing length at each [Ca2+]o and by the removal of a functional endocardium. Accordingly, the endocardium may help to control the performance of the heart by modulating peak contractile performance and relaxation of the underlying myocardium.

Carbonic anhydrase inhibition affects contraction of directly stimulated rat soleus

We have studied the contractile parameters of directly stimulated isolated rat soleus muscles incubated in media containing the carbonic anhydrase inhibitors chlorzolamide (5·10 −4M) or cyanate (10 −2M). Both inhibitors caused a decrease in isometric twitch and tetanic (5s) tensions and an increase in muscle relaxation time. It is speculated that among the three types of skeletal muscle carbonic anhydrase it may be the enzyme associated with the sarcoplasmatic reticulum whose inhibition caused the observed changes in contractile parameters.