EFFECTS OF PINACIDIL ON K-ARTERY VASCULAR SMOOTH-MUSCLE CELLS( CHANNELS IN HUMAN CORONARY)

We investigated pinacidil-activated K+ currents in vascular smooth mus cle cells (VSMC) from human coronary arteries with the patch-clamp met hod. In 19 of 54 VSMC, pinacidil (1 and 20 mu M) induced a large, nonr ectifying, outward current [IK(ATP)] and increased voltage-dependent o utward K+ currents [I-K(Ca)] positive to voltages of -25 mV. The pinac idil-induced (1 mu M) I-K(ATP) was blocked by glibenclamide (3 mu M) b ut was not affected by iberiotoxin (100-300 nM). Pinacidil activated u p to 150 functionally active ATP-dependent K+ channels (KATP channels) per cell with a single-channel conductance of similar to 17 pS at phy siological membrane potentials (between -80 and -30 mV) and K+ gradien ts (6 mM/130 mM). In 26 of 54 VSMC, on the other hand, pinacidil (1-20 mu M) failed to induce I-K(ATP) but increased I-K(Ca). This current w as completely blocked by iberiotoxin (100-300 nM) and tetraethylammoni um (1 mM) but not by glibenclamide (3 mu M). The single-channel conduc tance of the channel underlying I-K(Ca) was similar to 150 +/- 16 pS b etween -10 and +30 mV, consistent with large-conductance, maxi Ca2+- a ctivated, K+ channels (BKCa channels). We conclude that pinacidil is a nonselective K+ channel opener targeting K-ATP and BKCa channels. Fur thermore, the conductance of K-ATP channels in human coronary arteries is likely to be small under physiological conditions.