CA2-MUSCLE CELLS( ENTRY AND VASOCONSTRICTION DURING OSMOTIC SWELLING OF VASCULAR SMOOTH)

Exposure of aortic strips from guinea-pigs to hypotonic extracellular fluid is followed by marked vasoconstriction, which is inhibited by D- 600 (3 mu M), a blocker of voltage-sensitive Ca2+ channels. Convention al electrophysiology, patch-clamp studies, pH determination with 2', 7 ' bis(2-carboxyethyl)-5, 6-carboxyfluorescein (BCECF) and Ca2+ measure ments with Fura-2 have been performed on smooth muscle cells cultured either from rat or human aorta to further elucidate the underlying mec hanisms. Exposure of the cells to a 25% hypotonic extracellular fluid leads to a rapid and fully reversible depolarization, paralleled by an increase of the selectivity and conductance of the eel membrane to Cl -, an acidification of the cytoplasm and an increase of intracellular Ca2+ concentration ([Ca2+](i)). The latter is inhibited by the Ca2+ ch annel blocker D-600 (1-3 mu M). It is concluded that osmotic cell swel ling leads to the activation of an anion channel. The subsequent depol arization of the cell membrane activates voltage-sensitive Ca2+ channe ls which increases [Ca2+](i), thus stimulating the contraction of vasc ular smooth muscle cells.