Premium
Properties of the high‐conductance Ca 2+ ‐activated K + (BK) channel in pulmonary arterial smooth muscle cells (847.3)
Author(s) -
Detweiler Neil,
Song Li,
Versluis Rachel,
Nelson Piper,
Rhee Sung,
Rusch Nancy
Publication year - 2014
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.28.1_supplement.847.3
Subject(s) - bk channel , chemistry , protein subunit , activator (genetics) , vasodilation , biophysics , conductance , medicine , endocrinology , membrane potential , biology , biochemistry , physics , receptor , gene , condensed matter physics
We reported an upregulation of an oxygen‐insensitive splice variant of the high‐conductance Ca 2+ ‐activated K + (BK) channel in pulmonary arteries (PA) from rats with chronic hypoxia (CH)‐induced pulmonary hypertension (PH). This finding infers that the BK channel may represent a vasodilator target for the treatment of PH. However, the BK channel in pulmonary arterial smooth muscle cells (PASMCs) reportedly shows low Ca 2+ ‐sensitivity due to uncoupling of the α‐subunit pore from the requisite accessory β 1 subunit. The goal of this study was to: i) define the Ca 2+ ‐sensitivity of the BK channel in rat PASMC, and ii) evaluate if a BK channel opener that relies on the β 1 subunit activates BK channels in PASMCs. Whole‐cell K + current in patch‐clamped PASMCs from normoxic (N) and CH rats failed to reveal BK current, although it was observed under the same conditions in cerebral ASMCs. However, the Ca 2+ ‐sensitivity of BK channels in inside‐out patches from PASMCs and cerebral ASMCs exposed to a range of free Ca 2+ concentrations (10 ‐7 to 10 ‐4 mol/L) was not significantly different. Additionally, BK channel open probability (NPo) was increased 19‐fold by lithocholate (45 μmol/L), a BK channel activator that requires the β 1 subunit. Thus, the BK channel in PASMCs may be unique in some aspects, but it appears to show a normal level of Ca 2+ ‐sensitivity and be coupled to a functional β 1 subunit. Grant Funding Source : Supported by AHA 13PRE17240055 (NDD), NIH UL1RR029884 (NDD), gift from the Dean’s Society (UAMS COM)