The Effects of Sodium Pump Activity on the Slow Inward Current in Sheep Cardiac Purkinje Fibres

The effects of Na pump activity on the slow inward current, I_si, magnitude and twitch tension were investigated in sheep cardiac Purkinje fibres. A two-microelectrode voltage-clamp method was used, tension being measured simultaneously. Na pump activity was lowered either by reducing the extracellular K concentration, [K]_o, or by applying the cardiotonic steroid strophanthidin. Reduction of [K]_o from 4 to 0 mM leads to time-dependent increases in I_si magnitude and twitch tension. The increases of I_si and tension could be reversed by adding Tl, Rb, Cs or NH₄ ions to the K-free superfusate. The actions of these ions are attributed to the known ability of these cations to activate the external site of the Na pump. This conclusion is supported by the observation that such activator cations do not reverse the increases in I_si and tension produced by strophanthidin. We conclude that the effects of low [K]_o on I_si are mediated by Na pump inhibition. Similarly the Na pump inhibition produced by strophanthidin increases I_si and tension, although, in this case, other mechanisms may also contribute. Measurements of the activity of the electrogenic Na pump show that elevated intracellular Na ion concentration secondary to Na pump inhibition and not the instantaneous Na pump turnover rate mediates the increase in I_si magnitude.