Tension In Heart Muscle Research Articles

Role of Ca ++ channel in development of tension in heart muscle : Morad M, Cleeman L: J Mol Cell Cardiol 19:527–533,1987

Role of Ca ++ channel in development of tension in heart muscle : Morad M, Cleeman L: J Mol Cell Cardiol 19:527–533,1987

Role of Ca 2+ channel in development of tension in heart muscle

Role of Ca2+ Channel in Development of Tension in Heart Muscle. Journal of Molecular and Cellular Cardiology (1987) 19, 527-553. In mammalian and amphibian hearts Ca2+ enters the myocardial cells via voltage-gated Ca2+ channels. The role of Ca2+ channels in transporting the activator Ca2+ was probed by examining the redevelopment of tension and ICa in voltage-clamped myocardial strips after step recovery of Ca2+ channel from photolabile Ca2+ antagonist. Comparison of the kinetics of redevelopment of tension in the frog and mammalian heart following the photoinactivation of Ca2+ channel blockers showed that in the frog heart tension redevelops fully in one beat, while 5 to 7 beats were required for full redevelopment of tension in the mammalian heart. Ca2+ depletion studies using Antipyrylazo III showed that extracellular Ca2+ depletion during the action potential occurs primarily via the Ca2+ channel. In the frog heart sufficient Ca2+ is transported from the extracellular space during a single beat to activate tension. In the mammalian heart ICa triggers the release of internal stores, which when only fully loaded caused full development of tension. ICa also was involved in loading the intracellular Ca2+ pools. Two types of Ca2+ channels have been identified in the mammalian myocytes. The low-threshold rapidly inactivating Ca2+ channels appear to be involved in trigger release of Ca2+, while the high threshold (conventional Ca2+ channels) seem to be involved primarily in reloading of internal Ca2+ pools.

Effect of diltiazem on calcium transport and development of tension in heart muscle

Diltiazem relaxes vascular smooth muscle at concentrations as low as 10 −8 M . These concentrations do not affect either the action potential or the contractile activity of cardiac muscle. In this study the effect of diltiazem on excitation-contraction coupling processes in frog ventricular muscle was investigated. Diltiazem had little effect on the cardiac action potential or tension at concentrations less than 10 −7 M . At higher concentrations (10 −5 M ), the action potential shortened, the overshoot potential decreased, twitch tension was reduced, and the resting potential was unaffected. Potassium-chloride induced contractures were reduced by about 60 percent, suggesting that the effect of diltiazem was not due to the alteration in the action potential duration. In chemically skinned myocardium, the sensitivity of the myofilaments to calcium (Ca 2+ ) was not altered by diltiazem. The effects of diltiazem could be reversed in part either by increasing extracellular calcium or by adding epinephrine. Diltiazem (2 × 10 −6 M ) suppressed the tension-voltage relation under voltage clamp conditions. However, at even higher concentrations, significant tension could still be generated. Diltiazem reduced the slow inward current somewhat, but no direct relation could be found between suppression of the calcium-dependent inward current (I si ) and inhibition of tension. Diltiazem increased the late outward current but had no effect on the inwardly rectifying potassium (K + ) channel. In sodium (Na + )-depleted ventricular preparations, the tension-voltage relation, which reflects the voltage dependence of I si , is completely suppressed by diltiazem (2 × 10 −5 M ). These results suggest that diltiazem in large doses suppresses tension either by inhibition of a slowly inactivating Ca 2+ current or by modifying an undescribed step in excitation-contraction coupling processes.

Potassium chloride versus voltage clamp contractures in ventricular muscle.

In frog ventricle, developed tension was markedly larger in response to depolarization caused by a voltage clamp step than to depolarization induced by high concentrations of potassium chloride. Measurement of extracellular potassium activity at the surface and at the depth of muscle during the development of contractures showed that the diffusion of potassium is much slower than the spread of depolarization through the cross section of muscle. These two observations suggest that competition between the depolarizing and the negative inotropic effects of an increase in the extracellular potassium ion concentration may determine the time course and magnitude of contractile tension in heart muscle.

Effect of hyperosmolarity on resting and developed tension in heart muscle.

Simultaneous changes in weight, tension, and electrical activity were studied in the isolated perfused rabbit heart when the Ringer solution perfusion fluid was made hypertonic by the addition of sucrose, urea, glycerol, ethylene glycol, or formamide. The typical responses to each of the molecules was an initial drop in weight and tension followed by a return toward the base-line level. A 0.4 M concentration of sucrose, urea, or glycerol reduced the weight to 40 +/- 4.6, 48 +/- 3, and 52.2 +/- 3% of the initial value, respectively. The tension was simultaneously reduced to 23 +/- 3.5, 31 +/- 2, and 41 +/- 4% of its initial value. The tension drop produced by the solutes tested was linearly related to the amount of water lost by the heart. The falling phases of both tension and weight loss were closely correlated phases of both tension and weight loss were closely correlated in time a magnitude and were both related to the effectiveness of a particular molecule to move water out of the cells. In contrast, the subsequent rising phases of tension and weight were not as well correlated in time and magnitude. Whereas for most of the molecules used, the tension recovery was incomplete; urea, in contrast, caused an overshoot of the control tension level, thus pointing toward a unique inotropic effect of this compound. Resting tension rose for both urea and sucrose but not for the other compounds.

An effect of the cardiotoxic protein volvatoxin a on the function and structure of heart muscle cells

Volvatoxin-A, the heat labile cardiotoxin present in the mushroom Volvariella volvacea, causes a competitive, dose and time-dependent inhibition of the Ca 2+-accumulating activity of a sarcoplasmic-reticulum rich microsomal fraction isolated from guinea pig ventricular muscle. The inhibition is accompanied by an activation of the Ca 2+-dependent ATPase enzyme. Concentrations of toxin which inhibit the Ca 2+-transporting activity of the microsomes render them leaky to Ca 2+, but do not effect the rate of incorporation of P 32. Ten μg/ml toxin failed to alter the activity of the Na + + K +-activated, ouabain sensitive ATPase enzyme. It damaged the fine morphology of the mitochondria, inhibited the ability of isolated mitochondria to accumulate Ca 2+, and had little effect on the ability of isolated plasma membranes to bind Ca 2+. These findings may explain why volvatoxin A increases the diastolic resting tension in heart muscle.

Role of Na and Ca ions in the determination of isometrically developed tension of heart muscle.

Role of Na and Ca ions in the determination of isometrically developed tension of heart muscle.