Do the K+ channel openers relax smooth muscle by opening K+ channels?

During the past decade, a group of chemically heterogeneous compounds known as the K+ channel openers has emerged. These compounds open a certain class of K+ channels (ATP-sensitive K+ channels) in the sarcolemma of vascular smooth muscle cells, which leads to hyperpolarization of the cell membrane and relaxation of the tissue. The mechanisms by which hyperpolarization affects smooth muscle contraction and contractility can thus be examined. Hyperpolarization induced by these K+ channel openers prevents Ca2+ entry through voltage-operated Ca2+ channels. Surprisingly, and by mechanisms not yet defined, hyperpolarization of the cell also reduces agonist-induced accumulation of inositol 1,4,5-trisphosphate (and consequently, Ca2+ mobilization from intracellular stores), and the Ca2+ sensitivity of the contractile apparatus. In addition, recent evidence reviewed here by Ulrich Quast suggests that the K+ channel openers possess further mechanisms of vasorelaxation not linked to the opening of plasmalemmal K+ channels.