Cellular lithium uptake as a probe of sodium channels in the rat heart: modulation of lithium uptake by tetrodotoxin, verapamil, anthopleurin-A, isoproterenol and external stimulation.

Since the initial rate of sodium influx by the perfused rat heart is too rapid to measure accurately, lithium was used as an analogue for sodium. 10 mM lithium was added to the perfusate, and the rate of cellular lithium uptake was found to be linear for 5 min and was equal to 1.29 +/- 0.26 mumol/5 min/g wet wt heart. The cell took up lithium ions 36% as fast as sodium ions, but after 30 min the cellular/perfusate ratio of lithium reached nine times the cellular/perfusate ratio of sodium. Lithium uptake was inhibited 43% by 1 microM tetrodotoxin (TTX) (P greater than 0.05) and 47% by 1.4 microM verapamil (P less than 0.05). External stimulation abolished the inhibition by TTX. Anthopleurin-A (60 nM) stimulated TTX-sensitive lithium uptake by 118% (P less than 0.01) and stimulated verapamil-sensitive lithium uptake by 213% (P less than 0.01) but did not stimulate verapamil-sensitive manganese uptake. Anthopleurin-A also increased dP/dt by 164% (P less than 0.01). Isoproterenol (150 nM) stimulated both verapamil-sensitive lithium uptake (72%, P less than 0.01) and verapamil-sensitive manganese uptake (128%, P less than 0.01). This suggests that there are both TTX-sensitive and verapamil-sensitive sodium channels in the rat heart.