Selective block of swelling-activated Cl(-) channels over cAMP-dependent Cl(-) channels in ventricular myocytes.

摘要

The objective of this study on guinea-pig and rabbit ventricular myocytes was to evaluate the sensitivities of swelling-activated Cl(-) current (I(Cl(swell))) and cAMP-dependent cystic fibrosis transmembrane regulator (CFTR) Cl(-) current (I(Cl(CFTR))) to block by dideoxyforskolin and verapamil. The currents were recorded from whole-cell configured myocytes that were dialysed with a Cs(+)-rich pipette solution and superfused with either isosmotic Na(+)-, K(+)-, Ca(2+)-free solution that contained 140 mM sucrose or hyposmotic sucrose-free solution. Forskolin-activated I(Cl(CFTR)) was inhibited by reference blocker anthracene-9-carboxylic acid but unaffected by <==200 microM dideoxyforskolin and verapamil. However, dideoxyforskolin and verapamil had strong inhibitory effects on outwardly-rectifying, inactivating, distilbene-sensitive I(Cl(swell)); IC(50) values were approximately 30 microM, and blocks were voltage-independent and reversible. The results establish that dideoxyforskolin and verapamil can be used to distinguish between I(Cl(CFTR)) and I(Cl(swell)) in heart cells, and expand the pharmacological characterization of cardiac I(Cl(swell)).