Article,

Na$^+$/Ca$^2+$ exchange current in ventricular myocytes of fish heart: contribution to sarcolemmal Ca$^2+$ influx

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J. Exp. Biol., (July 1999)

Abstract

Influx of extracellular Ca$^2+$ plays a major role in the activation of contraction in fish cardiac cells. The relative contributions of Na$^+$/Ca$^2+$ exchange and L-type Ca$^2+$ channels to Ca$^2+$ influx are, however, unknown. Using a physiological action potential as the command pulse in voltage-clamped heart cells, we examined sarcolemmal Ca$^2+$ influx through Na$^+$/Ca$^2+$ exchange and L-type Ca$^2+$ channels in crucian carp (Carassius carassius L.) ventricular myocytes. When other cation conductances were blocked, a Ni2+-sensitive current with the characteristic voltage- and time-dependent properties of the Na$^+$/Ca$^2+$ exchange current could be distinguished. At the maximum overshoot voltage of the ventricular action potential (+40 mV; Na$^+$i=10 mmol l-1), the density of the Na$^+$/Ca$^2+$ exchange current was 2.99+/-0.27 pA pF-1 for warm-acclimated fish (23 degrees C) and 2.38+/-0.42 pA pF-1 for cold-acclimated fish (4 degrees C) (means +/- s.e.m., N=5-6; not significantly different, P=0.26). The relative contributions of the Na$^+$/Ca$^2+$ exchanger and L-type Ca$^2+$ channels to Ca$^2+$ influx were estimated using two partly different methods. Integration of the Ni2+-sensitive Na$^+$/Ca$^2+$ exchange current and the verapamil- and Cd2+-sensitive L-type Ca$^2+$ current suggests that, during the action potential, approximately one-third of the activating Ca$^2+$ comes through Na$^+$/Ca$^2+$ exchange and approximately two-thirds through L-type Ca$^2+$ channels. An alternative method of analysis, using the inward tail current as a measure of the total sarcolemmal Ca$^2+$ flux from which the Ni2+-sensitive Na$^+$/Ca$^2+$ exchange current was subtracted to obtain the Ca$^2+$ influx through the channels, suggests that L-type Ca$^2+$ channels and Na$^+$/Ca$^2+$ exchange are almost equally important in the activation of contraction. Furthermore, the time course of cell shortening is not adequately explained by sarcolemmal Ca$^2+$ influx through the channels alone, but is well approximated by the sum of Ca$^2+$ influx through the channels and the exchanger. The present results indicate that reverse Na$^+$/Ca$^2+$ exchange in crucian carp ventricular myocytes has sufficient capacity to trigger contraction and suggest that the exchange current makes a significant contribution to contractile Ca$^2+$ during the physiological action potential. The relative significance of channels and exchanger molecules in sarcolemmal Ca$^2+$ entry into crucian carp ventricular myocytes was unaffected by thermal acclimation when determined at 22 degrees C.

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