Ethanol-mediated relaxation of guinea pig urinary bladder smooth muscle

Involvement of BK and L-type Ca2+ channels

John Malysz, Serge A Y Afeli, Aaron Provence, Georgi Petkov

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Mechanisms underlying ethanol (EtOH)-induced detrusor smooth muscle (DSM) relaxation and increased urinary bladder capacity remain unknown. We investigated whether the large conductance Ca2+-activated K+ (BK) channels or L-type voltage-dependent Ca2+ 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 Ca2+ concentration ([Ca2+]), 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 [Ca2+], 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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume306
Issue number1
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

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Large-Conductance Calcium-Activated Potassium Channels
Smooth Muscle
Guinea Pigs
Urinary Bladder
Ethanol
Muscle Relaxation
Smooth Muscle Myocytes
Calcium-Activated Potassium Channels
Electrophysiology
Diuresis
Alcohols
Muscles
paxilline

All Science Journal Classification (ASJC) codes

  • Cell Biology
  • Physiology

Cite this

Ethanol-mediated relaxation of guinea pig urinary bladder smooth muscle : Involvement of BK and L-type Ca2+ channels. / Malysz, John; Afeli, Serge A Y; Provence, Aaron; Petkov, Georgi.

In: American Journal of Physiology - Cell Physiology, Vol. 306, No. 1, 01.01.2014.

Research output: Contribution to journalArticle

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title = "Ethanol-mediated relaxation of guinea pig urinary bladder smooth muscle: Involvement of BK and L-type Ca2+ channels",
abstract = "Mechanisms underlying ethanol (EtOH)-induced detrusor smooth muscle (DSM) relaxation and increased urinary bladder capacity remain unknown. We investigated whether the large conductance Ca2+-activated K+ (BK) channels or L-type voltage-dependent Ca2+ 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 Ca2+ concentration ([Ca2+]), 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 [Ca2+], 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.",
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AB - Mechanisms underlying ethanol (EtOH)-induced detrusor smooth muscle (DSM) relaxation and increased urinary bladder capacity remain unknown. We investigated whether the large conductance Ca2+-activated K+ (BK) channels or L-type voltage-dependent Ca2+ 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 Ca2+ concentration ([Ca2+]), 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 [Ca2+], 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.

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