GAP JUNCTIONAL COMMUNICATION AND VASCULAR SMOOTH-MUSCLE REACTIVITY - USE OF TETRAETHYLAMMONIUM CHLORIDE

Oscillatory contractions in uterine smooth muscle are mechanistically related to gap junction complex formation. We have tested the hypothes is that agonist-induced oscillations in vascular smooth muscle are als o mediated by gap junctions and that gap junctions are important for v ascular smooth muscle cell communication. Total RNA from cultured Wist ar-Kyoto rat (WKY) mesenteric arterial cells hybridized strongly with a cDNA probe for the message for connexin43, a monomer of the gap junc tion. In these same cells, the quaternary ion tetraethylammonium (TEA) (10 mM) increased Lucifer yellow dye transfer between contiguous cell s, a measure of cell-to-cell communication via gap junctions, approxim ately 35% above basal levels. Heptanol, an established inhibitor of ga p junction communication, completely blocked both basal- and TEA-stimu lated dye transfer between neighboring cells. In other experiments, he lical strips of superior mesenteric and tail arteries from WKY rats we re mounted in tissue baths for measurement of isometric contractile fo rce. TEA (10(-3)-10(-1) M) induced oscillatory contractions (1-5 cycle /min) in both mesenteric and tail arteries. Removal of endothelium did not affect the pattern of TEA-stimulated oscillations. Oscillations t o TEA were blocked in a concentration-dependent manner in both arterie s by heptanol (10(-7)-10(-3) M). Heptanol (10(-3) M) also significantl y reduced (40%) acetylcholine-induced relaxation in the mesenteric art ery (contracted with phenylephrine). Thus, these data document that: ( 1) the message for the gap junction protein connexin43 is located in c ultured arterial cells; (2) TEA induces oscillatory contractions in va scular smooth muscle and stimulates intercellular communication in cul tured cells, and (3) oscillatory contractions, vascular relaxation and intercellular communication are blocked by the gap junction inhibitor heptanol. Collectively, these data strongly support the importance of gap junctional communication in vascular smooth muscle reactivity, in cluding both oscillatory contractions and vascular relaxation.