Abstract
It is still controversial whether the cAMP-activated Cl − current ( I Cl,cAMP) is expressed in human cardiomyocytes. The whole-cell configuration of the voltage-clamp technique was used to examine in detail the I Cl,cAMP in single human atrial and ventricular myocytes. Human cardiomyocytes were enzymatically isolated from atrial or ventricular specimens obtained from open-heart surgery or cardiac transplantation, respectively. Isoproterenol (1 μM) or forskolin (10 μM) was used to activate the cAMP second-messenger system. The isoproterenol- or forskolin-induced Cl − current was elicited in 12 of 54 atrial myocytes but was completely absent from ventricular myocytes. The isoproterenol-induced Cl − current in atrial myocytes was time-independent and had a reversal potential close to zero. Endothelin-1 (30 nM) inhibited the isoproterenol-induced Cl − current by 75±6% ( n=4). This inhibitory effect of endothelin-1 was attenuated by pretreating atrial myocytes with the endothelin ET A receptor antagonist, BQ485, but not with the ET B receptor antagonist, BQ-788. The results provide evidence that the I Cl,cAMP exists in human atria, but not ventricle, and is inhibited by endothelin-1.
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