Distinct activity of BK channel beta(1)-subunit in cerebral and pulmonary artery smooth muscle cells

作者：Zheng Yun Min^*; Park Sang Woong; Stokes Lindsay; Tang Qiang; Xiao Jun Hua; Wang Yong Xiao

来源：American Journal of Physiology - Cell Physiology, 2013, 304(8): C780-C789.

DOI：10.1152/ajpcell.00006.2012

• big-conductance
• Ca2+-activated K+ channels
• patch-clamp recording
• gene knockout
• cerebral artery
• pulmonary artery

Zheng YM, Park SW, Stokes L, Tang Q, Xiao JH, Wang YX. Distinct activity of BK channel beta(1)-subunit in cerebral and pulmonary artery smooth muscle cells. Am J Physiol Cell Physiol 304: C780-C789, 2013. First published February 20, 2013; doi:10.1152/ajpcell.00006.2012.-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 beta(1)-subunits significantly reduced BK currents in CASMCs but had no effect in PASMCs. Western blotting experiments revealed that BK channel alpha-subunit protein expression level was comparable in CASMCs and PASMCs; however, beta(1)-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 beta(-/-)(1) mice. In contrast, pulmonary artery blood pressure was normal in beta(-/-)(1) 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 beta(1)-subunit function and contributes to diverse cellular responses in these two distinct types of cells.

• 出版日期2013-4