title: 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, 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 β(1)-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, β(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 β(1)(-/-) mice. In contrast, pulmonary artery blood pressure was normal in β(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 β(1)-subunit function and contributes to diverse cellular responses in these two distinct types of cells.
authors: Center for Cardiovascular Sciences, Albany Medical College, 47 New Scotland Ave., Albany, NY 12208, USA. zhengy@mail.ame.edu
authors: Yun-Min
authors: YM
authors: Zheng
authors: Sang Woong
authors: SW
authors: Park
authors: Lindsay
authors: L
authors: Stokes
authors: Qiang
authors: Q
authors: Tang
authors: Jun-Hua
authors: JH
authors: Xiao
authors: Yong-Xiao
authors: YX
authors: Wang
mesh_terms: D000818:Animals; D002536:Cerebral Arteries / Q000166:cytology / Q000378:metabolism*; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D010455:Peptides / Q000502:physiology; D011651:Pulmonary Artery / Q000166:cytology / Q000378:metabolism*
chemical_list: C545899:KCNMB1 protein, rat; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits; D010455:Peptides; C064719:iberiotoxin