Involvement of Na+-H+ Antiporter in Regulation of L-type Ca2+ Channel Current by Angiotensin II in Rabbit Ventricular Myocytes

The present study investigated the possible involvement of a Na-H antiporter in the regulation of L-type Ca channels by angiotensin II (Ang II) in isolated rabbit ventricular cardiac myocytes by using both cell-attached and whole-cell patch-clamp current recording techniques. In cell-attached patch-clamp current recordings, an increase in the open-state probability of the Ca channel (144.8±9.8% [mean±SEM], n=11) was seen after exposure of the cells to Ang II (100 nmol/L). This effect was inhibited by pretreatment with losartan (10 μmol/L), a synthetic antagonist of the AT1 receptor. 5-(N,N-Dimethyl)amiloride (100 μmol/L), an amiloride analogue, as well as Na-deficient bath solution abolished Ang II–induced stimulation of the Ca channel activities. In whole-cell patch-clamp current recordings, Ang II also increased the L-type Ca current when a pipette solution of pH 7.1 containing 5 mmol/L HEPES (139±5%, n=4) was used but did not significantly increase the current when a pipette solution of pH 7.5 containing 5 mmol/L HEPES or a pipette solution of pH 7.1 containing 30 mmol/L HEPES was used. These results suggest that Ang II–induced stimulation of the Ca channels is mediated by a Na-H antiporter and therefore provide a novel insight into signal transduction of Ang II receptor stimulation in cardiac myocytes.