Hyposmotic challenge inhibits inward rectifying K+ channels in cerebral arterial smooth muscle cells

This study sought to define whether inward rectifying K+ (KIR) channels were modulated by vasoactive stimuli known to depolarize and constrict intact cerebral arteries. Using pressure myography and patch-clamp electrophysiology, initial experiments revealed a Ba2+-sensitive KIR current in cerebral arterial smooth muscle cells that was active over a physiological range of membrane potentials and whose inhibition led to arterial depolarization and constriction. Real-time PCR, Western blot, and immunohistochemical analyses established the expression of both KIR2.1 and KIR2.2 in cerebral arterial smooth muscle cells. Vasoconstrictor agonists known to depolarize and constrict rat cerebral arteries, including uridine triphosphate, U46619, and 5-HT, had no discernable effect on whole cell KIR activity. Control experiments confirmed that vasoconstrictor agonists could inhibit the voltage-dependent delayed rectifier K+ (KDR) current. In contrast to these observations, a hyposmotic challenge that activates mechanos...