Strophanthidin and potassium on intracellular sodium activity in sheep heart

Double-barrelled sodium-selective microelectrodes were used to measure intracellular Na+ activity (aiNa) in sheep cardiac Purkinje fibres. A single rubber membrane gap voltage clamp controlled transmembrane potential (Vm) in some experiments. In quiescent preparations, the mean (+/- S.E.M.) aiNa was 8.9 +/- 0.3 mM (n = 46, Vm = -74.7 +/- 0.6 mV) at an extracellular potassium concentration [( K]o) of 5.4 mM and 7.5 +/- 0.4 mM (n = 37, Vm = -63.3 +/- 0.6 mV) at 10.8 mM [K]o. Brief strophanthidin exposures (5 X 10(-6) M for 6 to 10 mins) reversibly increased aiNa by 2 to 18 mM. The magnitude of this increase (delta aiNa) was similar in quiescent and paced (1 Hz) preparations but was inversely related to [K]o in the range studied (2.7, 5.4 and 10.8 mM). Voltage clamp experiments at a constant [K]o (5.4 or 10.8 mM) demonstrated a 27% lower delta aiNa at a Vm of -64 mV compared to -76 mV. In contrast, delta aiNa decreased by 48% when [K]o was increased from 5.4 to 10.8 mM with Vm held constant at either -64 or -76 mV. Hence, the observed antagonism between K+ ions and strophanthidin appeared to be due to a voltage-dependent effect and, to a greater extent, a specific ion-dependent effect. This latter finding is consistent with competitive behaviour between K+ ions and strophanthidin at the Na/K ATPase receptor.