Different effects of endothelin-1 on calcium and potassium currents in canine ventricular cells

Effects of endothelin-l (ET-1) on the L-type calcium current (I-Ca) and del ayed rectifier potassium current (I-K) were studied in isolated canine vent ricular cardiomyocytes using the whole-cell configuration of the patch-clam p technique. ET-1 (8 nM) was applied in three experimental arrangements: un treated cells, in the presence of 50 nM isoproterenol, and in the presence of 250 muM 8-bromo-cAMP. In untreated cells, ET-1 significantly decreased t he peak amplitude of I-Ca by 32.3 +/-4.8% at +5 mV (P<0.05) without changin g activation or inactivation characteristics of I-Ca. ET-1 had no effect on the amplitude of I-K, I-to (transient outward current) or I-K1 (inward rec tifier K current) in untreated cells; however, the time course of recovery from inactivation of I-to was significantly increased by ET-1 (from 26.5<pl us/minus>6 ms to 59.5 +/- 1.8 ms, P<0.05). Amplitude and time course of int racellular calcium transients, recorded in voltage-clamped cells previously loaded with the fluorescent calcium indicator dye Fura-2, were not affecte d by ET-1. ET-1 had no effect on force of contraction in canine ventricular trabeculae. Isoproterenol increased the amplitude of I-Ca to 263<plus/minus> 29% of con trol. ET-1 reduced I-Ca also in isoproterenol-treated cells by 17.8 +/-2% ( P<0.05); this inhibition was significantly less than obtained in untreated cells. I-K was increased by isoproterenol to 213<plus/minus>18% of control. This effect of isoproterenol on I-K was reduced by 31.8 +/-4.8% if the cel ls were pretreated with ET-1. Similarly, in isoproterenol-treated cells ET- 1 decreased I-K by 16.2 +/-1.5% (P<0.05). Maximal activation of protein kin ase A (PKA) was achieved by application of 8-bromo-cAMP in the pipette solu tion. In the presence of 8-bromo-cAMP ET-l failed to alter I-CA or I-K It w as concluded that differences in effects of ET-1 on I-CA and I-K may be rel ated to differences in cAMP sensitivity of the currents.