Role of Ca²⁺-activated K⁺ channels in acetylcholine-induced dilatation of the basilar artery in vivo

1. We tested the hypothesis that activation of large conductance calcium-activated potassium channels is involved in dilator responses of the basilar artery to acetylcholine in vivo. Using a cranial window in anaesthetized rats, we examined responses of the basilar artery to acetylcholine. 2. Topical application of acetylcholine (10^-6 and 10^-5 M) increased diameter of the basilar artery from 238 ± 7 μm to 268 ± 7 and 288 ± 7 μm, respectively (P < 0.05 vs. baseline diameter). Iberiotoxin (10^-8 M), an inhibitor of large conductance calcium-activated potassium channels, did not affect baseline diameter of the basilar artery. In the presence of 10^-8 M iberiotoxin, 10^-6 and 10^-5 M acetylcholine increased diameter of the basilar artery from 239 ± 7 μm to 246 ± 7 and 261 ± 7 μm, respectively. Thus, iberiotoxin attenuated acetylcholine-induced dilatation of the basilar artery (P < 0.05). 3. Sodium nitroprusside (10^-7 and 10^-6 M) increased diameter of the basilar artery from 242 ± 9 μm to 310 ± 12 and 374 ± 13 μm, respectively (P < 0.05 vs. baseline diameter). In the presence of iberiotoxin (10^-8 M), sodium nitroprusside (10^-7 and 10^-6 M) increased diameter of the basilar artery from 243 ± 6 μm to 259 ± 9 and 311 ± 12 μm, respectively. Thus, iberiotoxin attenuated dilator responses of the basilar artery to sodium nitroprusside (P < 0.05). 4. Iberiotoxin partly inhibited dilator responses of the basilar artery to forskolin, a direct activator of adenylate cyclase, but did not affect vasodilatation produced by levcromakalim, a potassium channel opener. 5. These results suggest that dilator responses of the basilar artery to acetylcholine and sodium nitroprusside are mediated, in part, by activation of large conductance calcium-activated potassium channels. Because both acetylcholine and sodium nitroprusside have been shown to activate guanylate cyclase via nitric oxide, activation of large conductance calcium-activated potassium channels may be one of the major mechanisms by which eyelid GMP causes dilatation of the basilar artery in vivo.