Effect of sodium on calcium-dependent force in unstimulated rat cardiac muscle.

It has previously been demonstrated that 1) changes in superfusate calcium concentration [Ca2+]o within the low millimolar range result in changes in "resting" force and in the light-scattering properties of unstimulated rat cardiac muscle, and 2) if [Ca2+]o is increased from zero to millimolar concentrations, i.e., reperfusion with Ca2+ after a Ca2+-free period, a large influx of Ca2+ occurs and is associated with a substantial increase in resting force. The present study determined whether the Ca2+ influx in either case was influenced by intracellular sodium (Na+i). In unstimulated isometric rat right ventricular papillary muscles equilibrated at 29 degrees C, [Ca2+]o was increased from 1 to 4 mM or from 0 to 2 mM under conditions that vary Na+i, and the resulting change in intracellular calcium concentration [( Ca2+]i) was monitored by changes in both resting force and the frequency of intensity fluctuations in laser light scattered by the muscle. In each case, lowering Na+i by equilibration in lowered extracellular sodium concentration [( Na+]o) or enhancing [Na+]i by equilibration in the absence of extracellular potassium or in the presence of ouabain markedly lowered and enhanced respectively the apparent Ca2+ influx in response to the step increase in [Ca2+]o. Thus, in unstimulated rat cardiac muscle, Na+i modulates the Ca2+ influx resulting from a step increase in [Ca2+]o both under physiological conditions and following a period of Ca2+-free superfusion, i.e., the "Ca2+ paradox." A passive influx of Ca2+ down its electrochemical gradient would not depend on Na+i, and the voltage-time dependent slow Ca2+o channel is inactivated under the experimental conditions employed. The results are best explained by a sarcolemmal Na+-Ca2+ exchange mechanism and suggest that the reversal potential of this electrogenic exchanger is exceeded during a step increase in [Ca2+]o even at the transmembrane potential of resting muscle.