THE EFFECTS OF ENDOTHELIN-1 ON THE PKA-DEPENDENT CL- CURRENT IN THE HEART

The effects of endothelin-1 (ET-1) on whole-cell cardiac PKA-dependent Cl- currents (I-Cl) were investigated using patch clamp techniques. E T-1 inhibited the isoproterenol-induced I-Cl with a half-maximally eff ective concentration of similar to 1 nM. ET-1 also inhibited the forsk olin-induced current in a similar concentration range. The effects of ET-1 were abolished by pre-treatment of the cells with pertussis toxin . Since ET-1 was ineffective at inhibiting the I-Cl induced by interna l dialysis with cyclic AMP, it is unlikely that the G(i)-protein had a direct effect on channel gating or phosphorylation of the channel by PKA. It is concluded that ET-1 inhibited the cardiac PKA-dependent I-C l by attenuating activation of adenylate cyclase and that this effect was mediated by a pertussis toxin-sensitive G-protein, presumably G(i) .