Inhibitory effect of endothelin-1 on the isoproterenol-induced chloride current in human cardiac myocytes

It is still controversial whether the cAAP-activated Cl- current (I-Cl,I-cA MP) is expressed in human cardiomyocytes. The whole-cell configuration of t he voltage-clamp technique was used to examine in detail the I-Cl,I-cAMP in single human atrial and ventricular myocytes. Human cardiomyocytes were en zymatically isolated from atrial or ventricular specimens obtained from ope n-heart surgery or cardiac transplantation, respectively. Isoproterenol (1 muM) or forskolin (10 muM) was used to activate the cAMP second-messenger s ystem. The isoproterenol- or forskolin-induced Cl- current was elicited in 12 of 54 atrial myocytes but was completely absent from ventricular myocyte s. The isoproterenol-induced Cl- current in atrial myocytes was time-indepe ndent and had a reversal potential close to zero. Endothelin-1 (30 nM) inhi bited the isoproterenol-induced Cl- current by 75 +/-6% (n = 4). This inhib itory effect of endothelin-1 was attenuated by pretreating atrial myocytes with the endothelin ETA receptor antagonist, BQ485, but not with the ETB re ceptor antagonist, BQ-788. The results provide evidence that the I-Cl,I-cAM P exists in human atria, but not ventricle, and is inhibited by endothelin- 1. (C) 2001 Elsevier Science B.V. All rights reserved.