Selective block of swelling-activated Cl^- channels over cAMP-dependent Cl^- channels in ventricular myocytes

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⁺-, Ca²⁺-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 μM dideoxyforskolin and verapamil. However, dideoxyforskolin and verapamil had strong inhibitory effects on outwardly-rectifying, inactivating, distilbene-sensitive I_Cl(swell); IC₅₀ values were ≈30 μM, 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).