Swelling‐induced Cl− current in guinea‐pig atrial myocytes: inhibition by glibenclamide

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Abstract
Whole‐cell currents were recorded from guinea‐pig atrial myocytes using the patch‐clamp technique under conditions designed to block K+ channels, Ca2+ channels and electrogenic transporters. Exposure of atrial myocytes to the hyposmotic external solution (Na+ reduction to about 70% of control) resulted in hyposmotic cell swelling which was associated with activation of an outwardly rectifying Cl− current (ICl,swell). Whereas the activation of ICl,swell was not significantly affected by replacement of ATP in the pipette solution with the non‐hydrolysable ATP analogue 5′‐adenylyl‐imidodiphosphate (AMP‐PNP), its activation was greatly reduced in cells dialysed with an ATP‐free pipette solution, thus indicating that the activation process of ICl,swell requires the presence of intra‐cellular ATP, but not its hydrolysis. Bath application of glibenclamide produced a concentration‐dependent block of ICl,swell with a half‐maximal inhibitory concentration (IC50) of 60.0 μm and a Hill coefficient of 2.1. The maximal effect (100% inhibition) was obtained with 500 μm glibenclamide. The steady‐state inhibition showed little voltage dependence, while glibenclamide at concentrations of more than 100 μm inhibited the outward ICl,swell more rapidly than the inward ICl,swell. The glibenclamide inhibition was fully reversible after removal of the drug, even when a maximal effect (full inhibition) was achieved at a high drug concentration (500 μm). These results show that (i) glibenclamide is one of the most potent inhibitors of guinea‐pig atrial ICl,swell and (ii) atrial ICl,swell and the cystic fibrosis transmembrane conductance regulator (CFTR) Cl− currents are almost equally sensitive to inhibition by glibenclamide.