Transmembrane Movement of Lithium Ions in Isolated Sheep Heart Purkinje Fibres

The many routes by which Li can cross the cardiac sarcolemma were examined using Li-selective microelectrodes. In the presence of 70 mmol /l extracellular Li there was a rapid increase in intracellular Li activity (a i Li) equivalent to an influx of 0.45 mmol /l /min (or 2.1 pmol /cm 2 ·s). Depolarisation (voltage-clamp or high [K ] o) had no significant effect on the rate of a i Liincrease, or recovery on removal of Li o. Following addition of 20 mmol /l [Li ] oto the normal Tyrode, the rate of a i Liincrease was stimulated by 49.7 % by removal of extracellular Mg. However Li entry was inhibited by SITS (100 μmol /l) by 20.6 %; tetrodotoxin (10 −5g /ml) 20.0 %; caesium (2 mmol /l) 22.5 %; verapamil (20 μmol /l) 14.3 %; and manganese (1 mmol /l) 37.6 %. With 5 mmol /l [Li ] o, a i Listabilized at 2.3 mmol /l, i.e. much lower than expected assuming passive distribution of Li (predicted level 61 mmol /l), implying active extrusion of Li from the cells. This stable level of Li was not significantly affected by short exposures to strophanthidin, bumetanide, or ethyl isopropylamiloride, but was decreased by increasing the [Ca ] oor adding manganese. The a i Liwas increased on removal of [Na ] oor addition of phloretin (100 μmol /l) suggesting that Na o-Li iexchange helps to maintain a low a i Li. The removal of K oproduced an increase in a i Li. This effect was inhibited by strophanthidin, suggesting Li can enter via the Na /K pump in K-free conditions.