Effects of elevating [Na] on membrane currents of canine ventricular myocytes: role of intracellular Ca ions

OBJECTIVES: Our first objective was to study how elevating [Na]i can modify the background membrane conductance in canine ventricular myocytes (CVM). In particular, we wanted to find evidence for a Nai-activated K current (IK,Na) in these cells. The second objective was to compare the effects of elevating [Na]i on membrane currents without and with intracellular Ca buffering. METHODS: Whole-cell currents were recorded and [Na]i was elevated either by using a pipette perfusion device that allowed [Na] in the pipette solution to be varied (from 0 to 50 mM), or by 50 microM ouabain. RESULTS: Although an outward current attributable to IK,Na was confirmed in guinea-pig ventricular myocytes (GPVM) under our recording conditions, no such current was seen in 29 CVM examined. With Cai buffering, the main effect of elevating [Na]i on CVM was an increase in inward current around and negative to the resting membrane potential. Based on the dependence of this Nai-induced inward current on K ions and its pharmacological properties, especially the effects of low concentrations of external Ba ions (< or = 5 microM) at strongly hyperpolarized voltages, we hypothesize that this current was carried by extracellular K ions through the inward rectifier (IK1) channels that had been modified by the high level of [Na]i. With Cai buffering, elevating [Na]i by ouabain had few or no effects on the L-type Ca channel current (ICa) or the slow delayed rectifier current (IKs). Without Cai buffering, ouabain induced a rapid reduction of both currents along with an increase in a time-independent outward current at voltages positive to -60 mV. CONCLUSION: Our data suggest that there are species variations in K channel expression and/or K channel modulation by intracellular Na ions. Furthermore, intracellular Ca ions play a crucial role in mediating the effects of Nai loading on membrane currents in canine ventricular myocytes.