Mechanism of biphasic contractions in strontium-treated ventricular muscle.

Abstract

SUMMARY. Biphasic contractions were produced in dog trabeculae by replacing 90-95% of the calcium in the bathing solution with strontium. These conditions produced prolonged action potentials accompanied by contractions with two distinct phasic components. The early component disappeared slowly when the remaining Ca ++ was removed, whereas the late component was eliminated quickly when Sr ++ was removed. Manganese ion (0.25 ITIM) preferentially decreased the late component without changing the action potential, whereas caffeine and ryanodine decreased or eliminated the early component. Ryanodine did not alter the action potential. Isoproterenol rapidly increased the early component and, more slowly and to a lesser degree, increased the late component. The results suggest that the early component is caused by intracellular release of activator cation, probably from the sarcoplasmic reticulum, whereas the late component is the result of Sr ++ entry across the sarcolemma, possibly by way of the slow inward current. TWO distinct components of contraction, one fast and one slow, have been shown to exist in mammalian ventricular myocardium under certain conditions. They can be seen in rested state contractions, after a 10-to 15-minute stimulation-free period, in the absense (Allen et al., 1976) or in the presence of an adrenergic agonist (Berescewicz and Reuter, 1977;Seibel et al., 1978), in low-temperature, constant frequency contractions under the influence of noradrenaline (Bogdanov et al., 1979), and after 90% replacement of Ca ++ with Sr ++ (Braveny and Sumbera, 1972). The common characteristic of these conditions is an increase in the duration of the action potential, and, in fact, biphasic contractions can be produced when the plateau of the action potential is lengthened by voltage clamp techniques (Morad and Trautwein, 1968;Braveny and Sumbera, 1970) or by toxins (Coraboeuf et al., 1975;Honerjager and Reiter, 1975). Although it is generally agreed that each component of contraction is due to a specific type of cation release, the site of the cation pools is the subject of some controversy.A number of proposals of the origin of the two cation release sites have been published, one visualizing Ca release from the same site but by different mechanisms (Allen et al., 1976) and the others hypothesizing contractile activation by two morphologically distinct pools (Braveny and Sumbera, 1972; Berescewicz and Reuter, 1977;Seibel et al., 1978;Bogdanov et al., 1979). The present study was designed to try to resolve the question of the origin of biphasic contractions by using specific pharmacological interventions. Strontium-induced resolution of the two components was used because it allows constant, relatively high frequency (0.5 Hz) stimulation while enabling a quantitative comparison of the effects of adrenergic agonists on the separate components to be made. The results are discussed in relation to the other models of two-component contractions. Methods Mechanical ExperimentsMongrel dogs (3-10 kg) of either sex wer...

Contractions in guinea‐pig ventricular myocytes triggered by a calcium‐release mechanism separate from Na+ and L‐currents.

“…The release mechanism described in this paper may be identical to the first component of biphasic contractions in multicellular preparations (Braveny & Sumbera, 1972;King & Bose, 1983;Reiter et al 1984;Honore et al 1987a, b;Vierling, 1988). The release component of biphasic contractions was also shown to be sensitive to ryanodine but not blocked by agents which inhibit L-type Ca2+ channels (King & Bose, 1983;Reiter et al 1984;Honore et al 1987 b;Vierling, 1988 existence of a ryanodine-sensitive Ca2+-release mechanism that operated independently of L-current. Interestingly, in these experiments the component of contraction which was inhibited by L-channel blockers was not inhibited by ryanodine (King & Bose, 1983;Vierling, 1988) as also reported in the present study.…”

“…The release component of biphasic contractions was also shown to be sensitive to ryanodine but not blocked by agents which inhibit L-type Ca2+ channels (King & Bose, 1983;Reiter et al 1984;Honore et al 1987 b;Vierling, 1988 existence of a ryanodine-sensitive Ca2+-release mechanism that operated independently of L-current. Interestingly, in these experiments the component of contraction which was inhibited by L-channel blockers was not inhibited by ryanodine (King & Bose, 1983;Vierling, 1988) as also reported in the present study. Clearly other studies have found that contractions elicited from a holding potential of -40 mV are sensitive to ryanodine.…”

“…Partial replacement of external Ca2+ with Sr2+ (Braveny & Sumbera, 1972) reveals biphasic contractions composed of an early component which can be inhibited by ryanodine and a late component which is more sensitive to the Ca2+ channel antagonist Mn2+ (King & Bose, 1983). In other studies, similar biphasic contractions were induced by partial membrane depolarization in potassium-rich solutions containing f8-adrenergic agonists (Reiter, Vierling & Seibel, 1984;Honore, Adamantidis, Dupuis, Challice & Guilbault, 1987a, b).…”

Positive inotropic effect of porcine left ventricular extract on canine ventricular muscle

“…Hence it is reasonable to hypothesize that the inotropic response may also be produced by the inhibition of Na', K+-ATPase and subsequent effect on Na'-Ca2+ exchange and elevation of intracellular Ca2". In support of our hypothesis, the studies on biphasic contraction have indicated that the extract primarily increases the delayed slow component (P2), which is caused by divalent cation entry across sarcolemma (King & Bose, 1983). The extract also increased the amplitude of the early component (although to a smaller extent than P2).…”

“…Biphasic contraction Biphasic contraction in canine trabeculae was produced as described by King & Bose (1983). Trabeculae were equilibrated in KH solution by stimulating at 0.5 Hz for 1 hour.…”