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Ion channel mechanisms underlying ethanol‐mediated relaxation in detrusor smooth muscle
Author(s) -
Malysz John,
Afeli Serge A.Y.,
Petkov Georgi V.
Publication year - 2013
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.27.1_supplement.923.8
Subject(s) - bk channel , chemistry , biophysics , conductance , patch clamp , ion channel , contraction (grammar) , electrophysiology , medicine , endocrinology , membrane potential , biochemistry , biology , receptor , physics , condensed matter physics
Various ion channels are affected by ethanol (EtOH). EtOH evokes relaxation of detrusor smooth muscle (DSM) and increases urinary bladder volume, but the underlying mechanisms remain unknown. In this study, we investigated whether the large conductance Ca 2+ ‐activated K + (BK) and L‐type voltage‐gated Ca 2+ channels, key regulators of DSM function, are the molecular targets for EtOH in guinea pig DSM. Experiments were conducted using patch‐clamp electrophysiology (whole‐cell and single‐channel) and DSM contractions. EtOH at 0.3% (~50 mM) enhanced outward K + currents at ≥ +20 mV that were attenuated by the selective BK channel blocker paxilline. In excised patches, EtOH (0.1–0.3%) increased single BK channel open probability, number of events and open dwell‐time constants without altering amplitude and mean single channel conductance. In DSM isolated strips, EtOH (0.03–0.1%) inhibited 20 mM KCl‐evoked phasic contraction frequency and at 0.3% also the amplitude and force; these effects were attenuated by paxilline. EtOH at 1% evoked similar relaxation in the presence and absence of paxilline and reduced L‐type voltage‐gated Ca 2+ channel currents. In summary, our study reveals involvement of BK and L‐type Ca 2+ channels in mediating the effects of EtOH in DSM causing relaxation and increase in bladder volume accommodating alcohol‐induced diuresis. Supported by NIH DK084284 to GVP and USC ASPIRE‐I to JM and GVP.