Activation thresholds of K_v, BK and CL_ca channels in smooth muscle cells in pial precapillary arterioles

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 BK channels 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.