Characterization of potassium currents modulated by BRL 38227 in rat portal vein

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Abstract
1 Smooth muscle cells of the rat portal vein were dispersed by enzymatic treatment and recordings of whole-cell membrane potassium currents were made by the voltage-clamp technique. In isolated cells by use of combined voltage- and current-clamp the effect of BRL 38227 on membrane potential and ionic currents was also studied. 2 BRL 38227 (0.1 to 10 μm) induced a non-inactivating potassium current (IKCO) which developed slowly (900 s to 300 s, respectively) to its full size. These effects of BRL 38227 were reversible. 3 In addition to its K-channel opening properties, BRL 38227 (1 to 10 μm) inhibited the amplitude and changed the activation and inactivation characteristics of a slowly-inactivating, calcium influx-independent, outward potassium current (ITO). 4 Application of stationary fluctuation analysis to IKCO, showed a mean single channel current of 0.65 pA at −10 mV under a quasi-physiological potassium gradient. 5 In a combined voltage-clamp/current-clamp configuration, BRL 38227 (1 μm) induced a mean hyperpolarization of 22 mV. 6 The induction of IKCO by BRL 38227 and the associated hyperpolarization were suppressed by glibenclamide (1 to 10 μm) in a concentration-dependent manner. Glibenclamide (1 μm) had no effect on the inhibition of ITO by BRL 38227 (1 μm).