The effects of nifedipine and other calcium antagonists on the glibenclamide‐sensitive K+ currents in smooth muscle cells from pig urethra

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Abstract
The effects of nifedipine on both levcromakalim‐induced membrane currents and unitary currents in pig proximal urethra were investigated by use of patch‐clamp techniques (conventional whole‐cell configuration and cell‐attached patches). Nifedipine had a voltage‐dependent inhibitory effect on voltage‐dependent Ba2+ currents at −50 mV (Ki=30.6 nM). In current‐clamp mode, subsequent application of higher concentrations of nifedipine (30 μM) caused a significant depolarization even after the membrane potential had been hyperpolarized to approximately −82 mV by application of 100 μM levcromakalim. The 100 μM levcromakalim‐induced inward current (symmetrical 140 mM K+ conditions, −50 mV) was inhibited by additional application of three different types of Ca antagonists (nifedipine, verapamil and diltiazem, all at 100 μM). In contrast, Bay K 8644 (1 μM) possessed no activating effect on the amplitude of this glibenclamide‐sensitive current. When 100 μM nifedipine was included in the pipette solution during conventional whole‐cell recording at −50 mV, application of levcromakalim (100 μM) caused a significant inward membrane current which was suppressed by 5 μM glibenclamide. On the other hand, inclusion of 5 μM glibenclamide in the pipette solution prevented levcromakalim from inducing an inward membrane current. The levcromakalim‐induced K+ channel openings in cell‐attached configuration were suppressed by subsequent application of 5 μM glibenclamide but not of 100 μM nifedipine. These results suggest that in pig proximal urethra, nifedipine inhibits the glibenclamide‐sensitive 43 pS K+ channel activity mainly through extracellular blocking actions on the K+ channel itself. British Journal of Pharmacology (1998) 123, 1601–1608; doi:10.1038/sj.bjp.0701777