Distinct activity of BK channel β1-subunit in cerebral and pulmonary artery smooth muscle cells

Abstract

This study was designed to test a hypothesis that the functional activity of big-conductance, Ca2+-activated K+ (BK) channels is different in cerebral and pulmonary artery smooth muscle cells (CASMCs and PASMCs). Using patch-clamp recordings, we found that the activity of whole cell and single BK channels were significantly higher in CASMCs than in PASMCs. The voltage and Ca2+ sensitivity of BK channels were greater in CASMCs than in PASMCs. Targeted gene knockout of β1-subunits significantly reduced BK currents in CASMCs but had no effect in PASMCs. Western blotting experiments revealed that BK channel α-subunit protein expression level was comparable in CASMCs and PASMCs; however, β1-subunit protein expression level was higher in CASMCs than in PASMCs. Inhibition of BK channels by the specific blocker iberiotoxin enhanced norepinephrine-induced increase in intracellular calcium concentration in CASMCs but not in PASMCs. Systemic artery blood pressure was elevated in β1−/− mice. In contrast, pulmonary artery blood pressure was normal in β1−/− mice. These findings provide the first evidence that the activity of BK channels is higher in cerebral than in PASMCs. This heterogeneity is primarily determined by the differential β1-subunit function and contributes to diverse cellular responses in these two distinct types of cells.