Possible role of Na+–Ca2+ exchange in the regulation of contractility in isolated adult ventricular myocytes from rat and guinea pig

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Abstract
Action potentials and developed contractions of externally unloaded single ventricular myocytes isolated from adult rat and guinea pig hearts were recorded by means of an optical system for recording contractile activity during regular stimulation by microelectrodes. Under control conditions, the shortenings (twitches) in the rat myocytes were fully inhibited by 0.1 μM ryanodine, but they were rather insensitive to the Ca2+ blocker 0.2–0.5 μM nifedipine. In contrast, the contractions of the isolated guinea pig ventricular myocytes were greatly suppressed by 0.2–0.5 μM nifedipine (to + gradient was decreased by reducing [Na]o or by elevating [Na]i in the presence of veratridine, the twitch contractions were increased in both species. The effect of reduced [Na]o on twitch contractions was not affected by ryanodine in either type of myocytes, while nifedipine still fully abolished the twitches in the guinea pig cells, indicating a strong dependence of guinea pig contractions on Ca2+ influx. On the other hand, the effect of a reduced Na gradient by veratridine was more complex; the usual twitch (phasic component) was increased and it was followed by a second (tonic) component which relaxed only after the repolarization of the action potential. While the phasic component was decreased by nifedipine and ryanodine in the usual way (as in the controls), the sustained contractions (lasting up to several seconds) were ryanodine and nifedipine insensitive. Furthermore, the cardiomyocytes of both species exposed to strontium in place of external calcium still exhibited all the effects observed when reducing the Na+ gradient. These data indicated that Sr2+ transport may occur via various routes similar to those of Ca2+ transport, including the Na+–Sr2+ exchange. In addition, in the presence of SrCl2 the rat myocytes exhibited longer durations of action potentials and their contractions became insensitive to ryanodine (like the guinea pig cells). It is concluded that Na+–Ca2+ exchange probably does not directly contribute in a quantitative fashion to the activation of contractile activity under normal conditions, but when the Na+ gradient is decreased, especially by increasing [Na]i, the contractions could be increased severalfold via this mechanism in both the rat and guinea pig cardiomyocytes.Key words: excitation–contraction coupling, isolated cardiac myocytes, nifedipine, ryanodine, veratridine, reduced [Na]o, epinephrine, SrCl2.

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