REGULATION OF AMILORIDE-SENSITIVE NA-1 IN DISTAL NEPHRON CELLS( CHANNELS BY ENDOTHELIN)

We used patch-clamp methods to investigate the effects of basolateral endothelin-1 (ET-1) on the amiloride-sensitive Na+ channel in A6 dista l nephron cells. One hundred picomolar ET-1 decreased channel activity via an increase in mean time closed (P < 0.01, n = 10). Channel inhib ition by pM ET-1 was mimicked by an ET-B receptor agonist (P < 0.05, n = 7) and was prevented by ET-B antagonists (P = 0.14, it = 10) but no t by an ET-A antagonist (P < 0.05, n = 4). With the inhibitory ET-B re ceptor blocked, higher doses of ET-1 (10 nM) actually increased channe l activity through an increase in mean time open (P < 0.001, n = 12). The current-voltage relationship and the number of channels were not c hanged by basolateral ET-1 exposure. We conclude that 1) basolateral E T-1 regulates amiloride-sensitive Na+ channels; 2) binding of picomola r ET-1 to ET-B receptors inhibits, whereas the binding of nanomolar ET -1 to a different ET receptor (likely ET-A) stimulates, channel activi ty; and 3) these dose-dependent, distal nephron responses provide a po tential mechanism for the in vivo natriuresis and antinatriuresis obse rved in response to ''subpressor'' and ''pressor'' concentrations of E T-1, respectively.