Mechanisms underlying regional differences in the Ca²⁺ sensitivity of BK_Ca current in arteriolar smooth muscle

β1-Subunits enhance the gating properties of large-conductance Ca²⁺-activated K⁺ channels (BK_Ca) formed by α-subunits. In arterial vascular smooth muscle cells (VSMCs), β1-subunits are vital in coupling SR-generated Ca²⁺ sparks to BK_Ca activation, affecting contractility and blood pressure. Studies in cremaster and cerebral VSMCs show heterogeneity of BK_Ca activity due to apparent differences in the functional β1-subunit:α-subunit ratio. To define these differences, studies were conducted at the single-channel level while siRNA was used to manipulate specific subunit expression. β1 modulation of the α-subunit Ca²⁺ sensitivity was studied using patch-clamp techniques. BK_Ca channel normalized open probability (NP_o) versus membrane potential (V_m) curves were more left-shifted in cerebral versus cremaster VSMCs as cytoplasmic Ca²⁺ was raised from 0.5 to 100 μm. Calculated V_1/2 values of channel activation decreased from 72.0 ± 6.1 at 0.5 μm Ca²⁺_i to -89 ± 9 mV at 100 μm Ca²⁺_i in cerebral compared with 101 ± 10 to -63 ± 7 mV in cremaster VSMCs. Cremaster BK_Ca channels thus demonstrated an ∼2.5-fold weaker apparent Ca²⁺ sensitivity such that at a value of V_m of -30 mV, a mean value of [Ca²⁺]_i of 39 μm was required to open half of the channels in cremaster versus 16 μm[Ca²⁺]_i in cerebral VSMCs. Further, shortened mean open and longer mean closed times were evident in BK_Ca channel events from cremaster VSMCs at either -30 or 30 mV at any given [Ca²⁺]. β1-Subunit-directed siRNA decreased both the apparent Ca²⁺ sensitivity of BK_Ca in cerebral VSMCs and the appearance of spontaneous transient outward currents. The data are consistent with a higher ratio of β₁-subunit:α-subunit of BK_Ca channels in cerebral compared with cremaster VSMCs. Functionally, this leads both to higher Ca²⁺ sensitivity and NP_o for BK_Ca channels in the cerebral vasculature relative to that of skeletal muscle.