Role of inwardly rectifying K+ channels in K+-induced cerebral vasodilatation in vivo

We tested whether activation of inwardly rectifying K+ (Kir) channels, Na+- K+-ATPase, or nitric oxide synthase (NOS) play a role in K+-induced dilatat ion of the rat basilar artery in vivo. When cerebrospinal fluid [K+] was el evated from 3 to 5, 10, 15, 20, and 30 mM, a reproducible concentration-dep endent vasodilator response was elicited (change in diameter = 9 +/- 1, 27 +/- 4, 35 +/- 4, 43 +/- 12, and 47 +/- 16%, respectively). Responses to Kwere inhibited by similar to 50% by the Kir channel inhibitor BaCl2 (30 and 100 muM). In contrast, neither ouabain (1-100 muM, a Na+-K+-ATPase inhibit or) nor N-G-nitro-L-arginine (30 mM, a NOS inhibitor) had any effect on K+- induced vasodilatation. These concentrations of K+ also hyperpolarized smoo th muscle in isolated segments of basilar artery, and these hyperpolarizati ons were virtually abolished by 30 muM BaCl2. RT-PCR experiments confirmed the presence of mRNA for Kir2.1 in the basilar artery. Thus K+-induced dila tation of the basilar artery in vivo appears to partly involve hyperpolariz ation mediated by Kir channel activity and possibly another mechanism that does not involve hyperpolarization, activation of Na+-K+-ATPase, or NOS.