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

Malysz J, Afeli SA, Provence A, Petkov GV. Ethanol-mediated relaxation of guinea pig urinary bladder smooth muscle: involvement of BK and L-type Ca channels. Am J Physiol Cell Physiol 306: C45–C58, 2014. First published October 23, 2013; 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 -activated K (BK) channels or L-type voltage-dependent Ca 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 concentration ([Ca ]), 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 M but not 2 M intracellular [Ca ], 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 EtOHinduced urinary bladder relaxation accommodating alcohol-induced diuresis.