Ethanol-mediated relaxation of guinea pig urinary bladder smooth muscle: involvement of BK and L-type Ca2+ channels

• Published in: American Journal of Physiology: Cell Physiology 2014-01, Vol.306 (1), p.C45-C58
• Main Authors: Malysz, John, Afeli, Serge A Y, Provence, Aaron, Petkov, Georgi V
• Format: Article
• Language: English
• Subjects: Animals; Calcium Channels, L-Type - physiology; Dose-Response Relationship, Drug; Ethanol - pharmacology; Guinea Pigs; Large-Conductance Calcium-Activated Potassium Channels - physiology; Male; Membrane Potentials - drug effects; Membrane Potentials - physiology; Muscle Relaxation - drug effects; Muscle Relaxation - physiology; Muscle, Smooth - drug effects; Muscle, Smooth - physiology; Organ Culture Techniques; Urinary Bladder - drug effects; Urinary Bladder - physiology
• ISSN: 0363-6143; 1522-1563
• DOI: 10.1152/ajpcell.00047.2013

Mechanisms underlying ethanol (EtOH)-induced detrusor smooth muscle (DSM) relaxation and increased urinary bladder capacity remain unknown. We investigated whether the large conductance Ca(2+)-activated K(+) (BK) channels or L-type voltage-dependent Ca(2+) channels (VDCCs), major regulators of DSM excitability and contractility, are targets for EtOH by patch-clamp electrophysiology (conventional and perforated whole cell and excised patch single channel) and isometric tension recordings using guinea pig DSM cells and isolated tissue strips, respectively. EtOH at 0.3% vol/vol (~50 mM) enhanced whole cell BK currents at +30 mV and above, determined by the selective BK channel blocker paxilline. In excised patches recorded at +40 mV and ~300 nM intracellular Ca(2+) concentration ([Ca(2+)]), EtOH (0.1-0.3%) affected single BK channels (mean conductance ~210 pS and blocked by paxilline) by increasing the open channel probability, number of open channel events, and open dwell-time constants. The amplitude of single BK channel currents and unitary conductance were not altered by EtOH. Conversely, at ~10 μM but not ~2 μM intracellular [Ca(2+)], EtOH (0.3%) decreased the single BK channel activity. EtOH (0.3%) affected transient BK currents (TBKCs) by either increasing frequency or decreasing amplitude, depending on the basal level of TBKC frequency. In isolated DSM strips, EtOH (0.1-1%) reduced the amplitude and muscle force of spontaneous phasic contractions. The EtOH-induced DSM relaxation, except at 1%, was attenuated by paxilline. EtOH (1%) inhibited L-type VDCC currents in DSM cells. In summary, we reveal the involvement of BK channels and L-type VDCCs in mediating EtOH-induced urinary bladder relaxation accommodating alcohol-induced diuresis.