VOLTAGE-DEPENDENT AND TIME-DEPENDENT K-PIG SMALL-INTESTINE( CHANNEL CURRENTS IN THE BASOLATERAL MEMBRANE OF VILLUS ENTEROCYTES ISOLATED FROM GUINEA)

Patch-clamp studies were carried out in villus enterocytes isolated fr om the guinea pig proximal small intestine. In the whole-cell mode, ou tward K+ currents were found to be activated by depolarizing command p ulses to -45 mV. The activation followed fourth order kinetics. The ti me constant of K+ current activation was voltage-dependent, decreasing from approximately 3 ms at a -10 mV to 1 ms at +50 mV. The K+ current inactivated during maintained depolarizations by a voltage-independen t, monoexponential process with a time constant of approximately 470 m s. If the interpulse interval was shorter than 30 s, cumulative inacti vation was observed upon repeated stimulations. The steady state inact ivation was voltage-dependent over the voltage range from -70 to -30 m V with a half inactivation voltage of -46 mV. The steady state activat ion was also voltage-dependent with a half-activation voltage of -22 m V. The K+ current profiles were not affected by chelation of cytosolic Ca2+. The K+ current induced by a depolarizing pulse was suppressed b y extracellular application of TEA+, Ba2+, 4-aminopyridine or quinine with half-maximal inhibitory concentrations of 8.9 mM, 4.6 mM, 86 muM and 26 muM, respectively. The inactivation time course was accelerated by quinine but decelerated by TEA+, when applied to the extracellular (but not the intracellular) solution. Extracellular (but not intracel lular) applications of verapamil and nifedipine also quickened the ina ctivation time course with 50% effective concentrations of 3 and 17 mu M, respectively. Quinine, verapamil and nifedipine shifted the steady state inactivation curve towards more negative potentials. Outward sin gle K+ channel events with a unitary conductance of approximately 8.4 pS were observed in excised inside-out patches of the basolateral memb rane, when the patch was depolarized to -40 mV. The ensemble current r apidly activated and thereafter slowly inactivated with similar time c onstants to those of whole-cell K+ currents. It is concluded that the basolateral membrane of guinea pig villus enterocytes has a voltage-ga ted, time-dependent, Ca2+-insensitive, small-conductance K+ channel. Q uinine, verapamil, and nifedipine accelerate the inactivation time cou rse by affecting the inactivation gate from the external side of the c ell membrane.