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The BK channel accessory β 1 subunit determines alcohol‐induced cerebrovascular constriction
Author(s) -
Bukiya An.,
Liu Jianxi,
Dopico Alejandro M.
Publication year - 2009
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2009.07.019
Subject(s) - bk channel , chemistry , constriction , biophysics , patch clamp , myocyte , conductance , potassium channel , medicine , endocrinology , membrane potential , biochemistry , biology , mathematics , combinatorics , receptor
Ethanol‐induced inhibition of myocyte large conductance, calcium‐ and voltage‐gated potassium (BK) current causes cerebrovascular constriction, yet the molecular targets mediating EtOH action remain unknown. Using BK channel‐forming (cbv1) subunits from cerebral artery myocytes, we demonstrate that EtOH potentiates and inhibits current atCa i 2 +lower and higher than ∼15 μM, respectively. By increasing cbv1's apparentCa i 2 +‐sensitivity, accessory BK β 1 subunits shift the activation‐to‐inhibition crossover of EtOH action to <3 μMCa i 2 +, with consequent inhibition of current under conditions found during myocyte contraction. Knocking‐down KCNMB1 suppresses EtOH‐reduction of arterial myocyte BK current and vessel diameter. Therefore, BK β 1 is the molecular effector of alcohol‐induced BK current inhibition and cerebrovascular constriction.