Ionic mechanism for contractile response to hyposmotic challenge in canine basilar arteries.

A hyposmotic challenge elicited contraction of isolated canine basilar arteries. The contractile response was nearly abolished by the removal of extracellular Ca(2+) and by the voltage-dependent Ca(2+) channel (VDCC) blocker nicardipine, but it was unaffected by thapsigargin, which depletes intracellular Ca(2+) stores. The contraction was also inhibited by Gd(3+) and ruthenium red, cation channel blockers, and Cl(-) channel blockers DIDS and niflumic acid. The reduction of extracellular Cl(-) concentrations enhanced the hypotonically induced contraction. Patch-clamp analysis showed that a hyposmotic challenge activated outwardly rectifying whole cell currents in isolated canine basilar artery myocytes. The reversal potential of the current was shifted toward negative potentials by reductions in intracellular Cl(-) concentration, indicating that the currents were carried by Cl(-). Moreover, the currents were abolished by 10 mM BAPTA in the pipette solution and by the removal of extracellular Ca(2+). Taken together, these results suggest that a hyposmotic challenge activates cation channels, which presumably cause Ca(2+) influx, thereby activating Ca(2+)-activated Cl(-) channels. The subsequent membrane depolarization is likely to increase Ca(2+) influx through VDCC and elicit contraction.