title: Inhibitory effect of endothelin-1 on the isoproterenol-induced chloride current in human cardiac myocytes.
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 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.
authors.affiliation: Department of Surgery, National Defense Medical Center, Taipei, Taiwan.
authors.forename: C S
authors.initials: CS
authors.lastname: Tsai
authors.forename: T H
authors.initials: TH
authors.lastname: Cheng
authors.forename: C I
authors.initials: CI
authors.lastname: Lin
authors.forename: J J
authors.initials: JJ
authors.lastname: Chen
authors.forename: F Y
authors.initials: FY
authors.lastname: Lee
authors.forename: C Y
authors.initials: CY
authors.lastname: Li
authors.forename: H J
authors.initials: HJ
authors.lastname: Hong
authors.forename: S H
authors.initials: SH
authors.lastname: Loh
mesh_terms: 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
chemical_list: D000318:Adrenergic beta-Agonists; D018118:Chloride Channels; D002712:Chlorides; D019332:Endothelin-1; D005576:Colforsin; D007545:Isoproterenol