author_facet Malysz, John
Afeli, Serge A. Y.
Provence, Aaron
Petkov, Georgi V.
Malysz, John
Afeli, Serge A. Y.
Provence, Aaron
Petkov, Georgi V.
author Malysz, John
Afeli, Serge A. Y.
Provence, Aaron
Petkov, Georgi V.
spellingShingle Malysz, John
Afeli, Serge A. Y.
Provence, Aaron
Petkov, Georgi V.
American Journal of Physiology-Cell Physiology
Ethanol-mediated relaxation of guinea pig urinary bladder smooth muscle: involvement of BK and L-type Ca2+ channels
Cell Biology
Physiology
author_sort malysz, john
spelling Malysz, John Afeli, Serge A. Y. Provence, Aaron Petkov, Georgi V. 0363-6143 1522-1563 American Physiological Society Cell Biology Physiology http://dx.doi.org/10.1152/ajpcell.00047.2013 <jats:p> Mechanisms underlying ethanol (EtOH)-induced detrusor smooth muscle (DSM) relaxation and increased urinary bladder capacity remain unknown. We investigated whether the large conductance Ca<jats:sup>2+</jats:sup>-activated K<jats:sup>+</jats:sup> (BK) channels or L-type voltage-dependent Ca<jats:sup>2+</jats:sup> 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<jats:sup>2+</jats:sup> concentration ([Ca<jats:sup>2+</jats:sup>]), 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<jats:sup>2+</jats:sup>], 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. </jats:p> Ethanol-mediated relaxation of guinea pig urinary bladder smooth muscle: involvement of BK and L-type Ca<sup>2+</sup> channels American Journal of Physiology-Cell Physiology
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series American Journal of Physiology-Cell Physiology
source_id 49
title Ethanol-mediated relaxation of guinea pig urinary bladder smooth muscle: involvement of BK and L-type Ca2+ channels
title_unstemmed Ethanol-mediated relaxation of guinea pig urinary bladder smooth muscle: involvement of BK and L-type Ca2+ channels
title_full Ethanol-mediated relaxation of guinea pig urinary bladder smooth muscle: involvement of BK and L-type Ca2+ channels
title_fullStr Ethanol-mediated relaxation of guinea pig urinary bladder smooth muscle: involvement of BK and L-type Ca2+ channels
title_full_unstemmed Ethanol-mediated relaxation of guinea pig urinary bladder smooth muscle: involvement of BK and L-type Ca2+ channels
title_short Ethanol-mediated relaxation of guinea pig urinary bladder smooth muscle: involvement of BK and L-type Ca2+ channels
title_sort ethanol-mediated relaxation of guinea pig urinary bladder smooth muscle: involvement of bk and l-type ca<sup>2+</sup> channels
topic Cell Biology
Physiology
url http://dx.doi.org/10.1152/ajpcell.00047.2013
publishDate 2014
physical C45-C58
description <jats:p> Mechanisms underlying ethanol (EtOH)-induced detrusor smooth muscle (DSM) relaxation and increased urinary bladder capacity remain unknown. We investigated whether the large conductance Ca<jats:sup>2+</jats:sup>-activated K<jats:sup>+</jats:sup> (BK) channels or L-type voltage-dependent Ca<jats:sup>2+</jats:sup> 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<jats:sup>2+</jats:sup> concentration ([Ca<jats:sup>2+</jats:sup>]), 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<jats:sup>2+</jats:sup>], 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. </jats:p>
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author Malysz, John, Afeli, Serge A. Y., Provence, Aaron, Petkov, Georgi V.
author_facet Malysz, John, Afeli, Serge A. Y., Provence, Aaron, Petkov, Georgi V., Malysz, John, Afeli, Serge A. Y., Provence, Aaron, Petkov, Georgi V.
author_sort malysz, john
container_issue 1
container_start_page 0
container_title American Journal of Physiology-Cell Physiology
container_volume 306
description <jats:p> Mechanisms underlying ethanol (EtOH)-induced detrusor smooth muscle (DSM) relaxation and increased urinary bladder capacity remain unknown. We investigated whether the large conductance Ca<jats:sup>2+</jats:sup>-activated K<jats:sup>+</jats:sup> (BK) channels or L-type voltage-dependent Ca<jats:sup>2+</jats:sup> 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<jats:sup>2+</jats:sup> concentration ([Ca<jats:sup>2+</jats:sup>]), 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<jats:sup>2+</jats:sup>], 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. </jats:p>
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spelling Malysz, John Afeli, Serge A. Y. Provence, Aaron Petkov, Georgi V. 0363-6143 1522-1563 American Physiological Society Cell Biology Physiology http://dx.doi.org/10.1152/ajpcell.00047.2013 <jats:p> Mechanisms underlying ethanol (EtOH)-induced detrusor smooth muscle (DSM) relaxation and increased urinary bladder capacity remain unknown. We investigated whether the large conductance Ca<jats:sup>2+</jats:sup>-activated K<jats:sup>+</jats:sup> (BK) channels or L-type voltage-dependent Ca<jats:sup>2+</jats:sup> 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<jats:sup>2+</jats:sup> concentration ([Ca<jats:sup>2+</jats:sup>]), 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<jats:sup>2+</jats:sup>], 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. </jats:p> Ethanol-mediated relaxation of guinea pig urinary bladder smooth muscle: involvement of BK and L-type Ca<sup>2+</sup> channels American Journal of Physiology-Cell Physiology
spellingShingle Malysz, John, Afeli, Serge A. Y., Provence, Aaron, Petkov, Georgi V., American Journal of Physiology-Cell Physiology, Ethanol-mediated relaxation of guinea pig urinary bladder smooth muscle: involvement of BK and L-type Ca2+ channels, Cell Biology, Physiology
title Ethanol-mediated relaxation of guinea pig urinary bladder smooth muscle: involvement of BK and L-type Ca2+ channels
title_full Ethanol-mediated relaxation of guinea pig urinary bladder smooth muscle: involvement of BK and L-type Ca2+ channels
title_fullStr Ethanol-mediated relaxation of guinea pig urinary bladder smooth muscle: involvement of BK and L-type Ca2+ channels
title_full_unstemmed Ethanol-mediated relaxation of guinea pig urinary bladder smooth muscle: involvement of BK and L-type Ca2+ channels
title_short Ethanol-mediated relaxation of guinea pig urinary bladder smooth muscle: involvement of BK and L-type Ca2+ channels
title_sort ethanol-mediated relaxation of guinea pig urinary bladder smooth muscle: involvement of bk and l-type ca<sup>2+</sup> channels
title_unstemmed Ethanol-mediated relaxation of guinea pig urinary bladder smooth muscle: involvement of BK and L-type Ca2+ channels
topic Cell Biology, Physiology
url http://dx.doi.org/10.1152/ajpcell.00047.2013