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Properties of the high‐conductance Ca 2+ ‐activated K + (BK) channel in pulmonary arterial smooth muscle cells
Author(s) -
Detweiler Neil,
Song Li,
McClenehan Samantha,
Kharade Sujay,
Kurten Richard,
Rhee Sung,
Rusch Nancy
Publication year - 2015
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.29.1_supplement.943.4
Subject(s) - bk channel , hypoxic pulmonary vasoconstriction , vasodilation , chemistry , hypoxia (environmental) , vasoconstriction , lung , endocrinology , pulmonary hypertension , medicine , vascular smooth muscle , biophysics , membrane potential , smooth muscle , biology , biochemistry , oxygen , organic chemistry
Pulmonary hypertension (PH) is associated with a loss of vasodilator influences in the pulmonary circulation, which results in pathogenic vasoconstriction. However, we observed an over‐expression of high‐conductance, Ca 2+ ‐activated K + (BK) channels in pulmonary arteries (PA) during chronic hypoxia (CH)‐induced PH, providing a potential vasodilator target. Here, we report that BK channels of PA smooth muscle cells (PASMCs) from CH rats retain high Ca 2+ ‐sensitivity, α‐β 1 subunit coupling that confers sensitivity to BK channel openers, and hypoxia‐ in sensitivity as compared to normal (N) rats (n=4‐11). Importantly, these properties may permit pharmacological activation of the BK channel even in a hypoxic environment. In inside‐out membrane patches used to record unitary BK currents in PASMCs from CH rats (n= 4‐7), the BK channel log(Ca 2+ EC 50 (mol/L)) was ‐5.9 in both N and CH rats. Lithocholate (LCA), a BKβ 1 subunit‐dependent opener, caused a 26‐fold and 19‐fold increase in BK channel open‐state probability in PASMC from CH and N rats, respectively. Using lung samples from organ donors without diagnosed PH, we also defined BK channel properties in human PASMCs. Similar to rat, the h BK channel exhibited high Ca 2+ ‐sensitivity (log(Ca 2+ EC 50 (mol/L)) = ‐6.1), was activated by LCA, and was not inhibited by acute hypoxia (n=4‐7). Thus, PASMCs from N and CH rats and humans without diagnosed lung disease express a β 1 subunit‐coupled, hypoxia‐ in sensitive BK channel, which is responsive to BK channel openers. Supported by AHA 13PRE17240055 (NDD), NIH UL1RR029884 (NDD), and the UAMS College of Medicine Dean's Society.