Activation Thresholds of KV, BK andCl Ca Channels in Smooth Muscle Cells in Pial Precapillary Arterioles

Abstract

We have previously shown expression of voltage-gated K⁺ channels (K_V) 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 K_V 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 K_V channel current. Furthermore, in the absence of an exogenous vasoconstrictor agent, block of K_V channels but not BK or Cl^– channels caused constriction, although in the presence of endothelin-1 block of BK or K_V channels caused constriction. The data indicate K_V channels are the first inhibitory mechanism to activate when there is depolarisation in precapillary arteriolar smooth muscle cells of the cerebral circulation.