Inhibitory effect of endothelin-1 on the isoproterenol-induced chloride current in human cardiac myocytes.
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 microM) or forskolin (10 microM) 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.
Tsai
C S
CS
Department of Surgery, National Defense Medical Center, Taipei, Taiwan.
Cheng
T H
TH
Lin
C I
CI
Chen
J J
JJ
Lee
F Y
FY
Li
C Y
CY
Hong
H J
HJ
Loh
S H
SH
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000328:Adult; D000368:Aged; D016275:Atrial Function; D018118:Chloride Channels / Q000502:physiology*; D002712:Chlorides / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D019332:Endothelin-1 / Q000494:pharmacology*; D005260:Female; D006325:Heart Atria / Q000166:cytology / Q000187:drug effects*; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects*; D008875:Middle Aged; D013997:Time Factors; D016276:Ventricular Function
D000318:Adrenergic beta-Agonists; D018118:Chloride Channels; D002712:Chlorides; D019332:Endothelin-1; D005576:Colforsin; D007545:Isoproterenol