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Disrupted BK Ca Channel β1 Subunit Gene Contributes to Vascular Dysfunction in Pulmonary Hypertension
Author(s) -
Barnes Elizabeth A,
Chen Chihhsin,
Lee Lori,
Barnes Shayna L,
Cornfield David N
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.772.10
Subject(s) - vasoconstriction , medicine , bk channel , pulmonary hypertension , protein subunit , hypoxic pulmonary vasoconstriction , endocrinology , contraction (grammar) , arteriole , potassium channel , chemistry , cardiology , circulatory system , gene , biochemistry
BACKGROUND The BK Ca channel is a calcium‐sensitive potassium channel fundamental to the control of smooth muscle cell (SMC) tone. Loss of BK Ca channel function leads to membrane depolarization and vasoconstriction. Previous reports have shown that mice with a disrupted BK Ca channel β1 subunit have an increase in blood pressure and arterial tone in cerebral arteries. In addition, a gain‐of‐function β1 mutation, E65K, has been associated with low prevalence of diastolic hypertension, suggesting that the β1 subunit of the BK Ca channel is a key molecular component involved in vasoregulation. HYPOTHESIS It is unknown as to the role of the β1 subunit in modulating pulmonary vascular tone. To assess the contribution of the BK Ca channel β1 subunit in pulmonary vasoregulation, mice with a disrupted β1 gene (KCNMB1 −/− ) were examined. RESULTS KCNMB1 −/− mice exhibited significantly higher right ventricular systolic pressure (RVSP) compared to wild‐type (WT) littermates with exposure to acute or chronic hypoxia in the absence of histologic evidence of accentuated vascular remodeling. The β1 subunit was predominantly expressed in pulmonary arteriole SMC. Isolated peripheral PASMC promoted collagen gel contraction irrespective of β1 expression. Isolated KCNMB1 −/− PASMC exhibited significant increases in focal adhesions and Rho kinase expression compared to WT cells. CONCLUSIONS Compromised PASMC β1 function may contribute to the heightened vasoconstriction in the microvasculature that characterizes pulmonary hypertension.