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 (ICl(swell)) and cAMP-dependent cystic fibrosis transmembrane regulator (CFTR) Cl- current (ICl(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 ICl(CFTR) was inhibited by reference blocker anthracene-9-carboxylic acid but unaffected by < or = 200 microM dideoxyforskolin and verapamil. However, dideoxyforskolin and verapamil had strong inhibitory effects on outwardly-rectifying, inactivating, distilbene-sensitive ICl(swell); IC50 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 ICl(CFTR) and ICl(swell) in heart cells, and expand the pharmacological characterization of cardiac ICl(swell).
Shuba
Lesya M
LM
Department of Physiology and Biophysics, Dalhousie University, Halifax, Nova Scotia, Canada B3H 4H7.
Missan
Sergey
S
Zhabyeyev
Pavel
P
Linsdell
Paul
P
McDonald
Terence F
TF
D000818:Animals; D018118:Chloride Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000242:Cyclic AMP / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D011817:Rabbits
D018118:Chloride Channels; D000242:Cyclic AMP