INHIBITION OF DELAYED RECTIFIER K-CURRENT BY LEVCROMAKALIM IN SINGLE INTESTINAL SMOOTH-MUSCLE CELLS - EFFECTS OF CATIONS AND DEPENDENCE ON K+-FLUX()

1 Whole-cell voltage-clamp recordings were made from single smooth mus cle cells isolated from the longitudinal layer of the guinea-pig small intestine. 2 Levcromakalim ((-)Ckm) inhibited delayed rectifier K-cur rent (IK(DR)) and induced a voltage-independent K-current (I-K(-Ckm)) Both effects were inhibited similarly by glibenclamide. In some cells, however, I-K(-Ckm) could be induced without any effect on I-K(DR). 3 Ba2+ caused a voltage-dependent block of I-K(-Ckm). The IC50 was 0.2 m M at -40 mV (6 cells), but at 0 mV 2 mM Ba2+ caused only a 26 +/- 7% i nhibition (n = 5). Ba2+ had much less effect on I-K(DR), 2 mM Ba2+ hav ing no inhibitory effect on current elicited by depolarization to -30 mV (n = 6) or 0 mV (n = 5). 4 Low concentrations of Zn2+ blocked I-K(- Ckm) while having little effect on I-K(DR). Zn2+ (40 mu M) caused a 77 +/- 1% reduction of I-K(-Ckm) at -30 mV (n = 4) but I-K(DR) was inhib ited by only 10 +/- 3% at the same voltage (n = 4). 5 Inward current a mplitudes were compared in 135 mM Rb+ and 135 mM K+ bath solutions. (- )Ckm-activated Rb2+-current was only 4% of the K+-current, whereas del ayed rectifier Rb+-current was larger than K+-current. 6 (-)Ckm did no t inhibit I-K(DR) if I-K(-Ckm) was blocked. In the presence of 2 mM Ba 2+ or 135 mM Rb+, (-)Ckm did not induce current nor did it inhibit the delayed rectifier. When [Rb+](o) was 25 mM and [K+](i) was 130 mM, (- )Ckm elicited outward current and inhibited outward delayed rectifier current (at voltages positive of the reversal potential) but it did no t elicit inward current or inhibit inward delayed rectifier current (a t voltages negative of the reversal potential). 7 These experiments in dicate that (-)Ckm-activated K channels are more sensitive to inhibiti on by Ba2+ and Zn2+ and pass inward Rb+ current less well than delayed rectifier K channels. They also suggest that (-)Ckm does not modulate delayed rectifier K channels directly or via an intermediate protein but that the inhibitory effect of (-)Ckm on IK(DR) arises as a consequ ence of K+-flux through (-)Ckm-activated K channels.