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⁺]₀ 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⁺]₀ is increased from zero to millimolar concentrations, i.e., reperfusion with Ca²⁺ after 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°C, [Ca²⁺]₀ 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⁺]₀) 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⁺]₀. Thus, in unstimulated rat cardiac muscle, Na⁺(i) modulates the Ca²⁺ influx resulting from a step increase in [Ca²⁺]₀ 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⁺₀ 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⁺]₀ even at the transmembrane potential of resting muscle.