THE EFFECTS OF NIFEDIPINE AND OTHER CALCIUM-ANTAGONISTS ON THE GLIBENCLAMIDE-SENSITIVE K-MUSCLE CELLS FROM PIG URETHRA( CURRENTS IN SMOOTH)

1 The effects of nifedipine on both levcromakalim-induced membrane cur rents and unitary currents in pig proximal urethra were investigated b y use of patch-clamp techniques (conventional whole-cell configuration and cell-attached patches). 2 Nifedipine had a voltage-dependent inhi bitory effect on voltage-dependent Ba2+ currents at -50 mV (K-i = 30.6 nM). 3 In current-clamp mode, subsequent application of higher concen trations of nifedipine (greater than or equal to 30 mu M) caused a sig nificant depolarization even after the membrane potential had been hyp erpolarized to approximately -82 mV by application of 100 mu M levcrom akalim. 4 The 100 mu M levcromakalim-induced inward current (symmetric al 140 mM K+ conditions, -50 mV) was inhibited by additional applicati on of three different types of Ca antagonists (nifedipine, verapamil a nd diltiazem, all at 100 mu M). In contrast, Bay K 8644 (1 mu M) posse ssed no activating effect on the amplitude of this glibenclamide-sensi tive current. 5 When 100 mu M nifedipine was included in the pipette s olution during conventional whole-cell recording at -50 mV, applicatio n of levcromakalim (100 mu M) caused a significant inward membrane cur rent which was suppressed by 5 mu M glibenclamide. On the other hand, inclusion of 5 mu M glibenclamide in the pipette solution prevented le vcromakalim from inducing an inward membrane current. 6 The levcromaka lim-induced K+ channel openings in cell-attached configuration were su ppressed by subsequent application of 5 mu M glibenclamide but not of 100 mu M nifedipine. 7 These results suggest that in pig proximal uret hra, nifedipine inhibits the glibenclamide-sensitive 43 pS K+ channel activity mainly through extracellular blocking actions on the K+ chann el itself.