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 Ca2+ 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 Ca2+ 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 mu mol/L), a synthetic antagonist of the AT(1) receptor. 5-(N,N-Dimethyl)amiloride (100 mu mol/L), an amiloride analogue, as well as Na+-deficient bath solution abolished Ang II-induced stimulation of the Ca2+ channel activities. In whole-cell patch-clamp current recordings, Ang II also increased the L-type Ca2+ current when a pipette solution of pH 7.1 containing 5 mmol/L HEPES (139+/-15%, 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 Ca2+ 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.