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

First Author  Zheng YM Year  2013
Journal  Am J Physiol Cell Physiol Volume  304
Issue  8 Pages  C780-9
PubMed ID  23426969 Mgi Jnum  J:196390
Mgi Id  MGI:5487869 Doi  10.1152/ajpcell.00006.2012
Citation  Zheng YM, et al. (2013) Distinct activity of BK channel beta(1)-subunit in cerebral and pulmonary artery smooth muscle cells. Am J Physiol Cell Physiol 304(8):C780-9
abstractText  This study was designed to test a hypothesis that the functional activity of big-conductance, Ca(2+)-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 Ca(2+) 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.
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