We have previously shown expression of voltage-gated K+ channels (KV) in smooth muscle of cerebral arterioles and suggested the channels function to oppose voltage-dependent Ca2+ entry. However, other studies indicate that large conductance Ca2+-activated K+ (BK) channels serve this function and chloride (Cl) channels may have the opposite effect. In this study we compared the activation thresholds and absolute current amplitudes for KV channels, BK channels and Cl channels at physiological membrane potentials in intact precapillary arterioles from the rabbit cerebral circulation. Patch-clamp recordings were made to measure current and membrane potential, and a video scan line was used to detect external diameter. Two strategies to determine the basal current-voltage relationship of BKchannels showed the channels contributed current only at voltages positive of –35 mV, even though voltage-dependent Ca2+-entry occurred. Ca2+-activated and niflumic acid-sensitive Cl current was detected but, between –50 and –10 mV, both BK and Cl channel currents were much smaller and contributed less to the membrane potential compared with KV channel current. Furthermore, in the absence of an exogenous vasoconstrictor agent, block of KV channels but not BK or Cl channels caused constriction, although in the presence of endothelin-1 block of BK or KV channels caused constriction. The data indicate KV channels are the first inhibitory mechanism to activate when there is depolarisation in precapillary arteriolar smooth muscle cells of the cerebral circulation.

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