Regulation of Guinea Pig detrusor smooth muscle excitability by 17β-estradiol

The role of the large conductance voltage- and Ca2+-activated K+ channels

Aaron Provence, Kiril L. Hristov, Shankar P. Parajuli, Georgi Petkov

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Estrogen replacement therapies have been suggested to be beneficial in alleviating symptoms of overactive bladder. However, the precise regulatory mechanisms of estrogen in urinary bladder smooth muscle (UBSM) at the cellular level remain unknown. Large conductance voltage- and Ca2+-activated K+ (BK) channels, which are key regulators of UBSM function, are suggested to be non-genomic targets of estrogens. This study provides an electrophysiological investigation into the role of UBSM BK channels as direct targets for 17β-estradiol, the principle estrogen in human circulation. Single BK channel recordings on inside-out excised membrane patches and perforated whole cell patch-clamp were applied in combination with the BK channel selective inhibitor paxilline to elucidate the mechanism of regulation of BK channel activity by 17β-estradiol in freshly-isolated Guinea pig UBSM cells. 17β-Estradiol (100 nM) significantly increased the amplitude of depolarizationinduced whole cell steady-state BK currents and the frequency of spontaneous transient BK currents in freshly-isolated UBSM cells. The increase in whole cell BK currents by 17β- estradiol was eliminated upon blocking BK channels with paxilline. 17β-Estradiol (100 nM) significantly increased (∼3-fold) the single BK channel open probability, indicating direct 17β-estradiol-BK channel interactions. 17β-Estradiol (100 nM) caused a significant hyperpolarization of the membrane potential of UBSM cells, and this hyperpolarization was reversed by blocking the BK channels with paxilline. 17β-Estradiol (100 nM) had no effects on L-type voltage-gated Ca2+ channel currents recorded under perforated patch-clamp conditions. This study reveals a new regulatory mechanism in the urinary bladder whereby BK channels are directly activated by 17β-estradiol to reduce UBSM cell excitability.

Original languageEnglish (US)
Article number141950
JournalPloS one
Volume10
Issue number11
DOIs
StatePublished - Nov 4 2015

Fingerprint

Large-Conductance Calcium-Activated Potassium Channels
Calcium-Activated Potassium Channels
potassium channels
bladder
smooth muscle
guinea pigs
Smooth Muscle
Muscle
estradiol
Estradiol
Guinea Pigs
calcium
Urinary Bladder
Electric potential
myocytes
Smooth Muscle Myocytes
Estrogens
estrogens
Clamping devices
estrogen replacement therapy

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Regulation of Guinea Pig detrusor smooth muscle excitability by 17β-estradiol : The role of the large conductance voltage- and Ca2+-activated K+ channels. / Provence, Aaron; Hristov, Kiril L.; Parajuli, Shankar P.; Petkov, Georgi.

In: PloS one, Vol. 10, No. 11, 141950, 04.11.2015.

Research output: Contribution to journalArticle

@article{fd05673a996546229c97ca26abcc6d3b,
title = "Regulation of Guinea Pig detrusor smooth muscle excitability by 17β-estradiol: The role of the large conductance voltage- and Ca2+-activated K+ channels",
abstract = "Estrogen replacement therapies have been suggested to be beneficial in alleviating symptoms of overactive bladder. However, the precise regulatory mechanisms of estrogen in urinary bladder smooth muscle (UBSM) at the cellular level remain unknown. Large conductance voltage- and Ca2+-activated K+ (BK) channels, which are key regulators of UBSM function, are suggested to be non-genomic targets of estrogens. This study provides an electrophysiological investigation into the role of UBSM BK channels as direct targets for 17β-estradiol, the principle estrogen in human circulation. Single BK channel recordings on inside-out excised membrane patches and perforated whole cell patch-clamp were applied in combination with the BK channel selective inhibitor paxilline to elucidate the mechanism of regulation of BK channel activity by 17β-estradiol in freshly-isolated Guinea pig UBSM cells. 17β-Estradiol (100 nM) significantly increased the amplitude of depolarizationinduced whole cell steady-state BK currents and the frequency of spontaneous transient BK currents in freshly-isolated UBSM cells. The increase in whole cell BK currents by 17β- estradiol was eliminated upon blocking BK channels with paxilline. 17β-Estradiol (100 nM) significantly increased (∼3-fold) the single BK channel open probability, indicating direct 17β-estradiol-BK channel interactions. 17β-Estradiol (100 nM) caused a significant hyperpolarization of the membrane potential of UBSM cells, and this hyperpolarization was reversed by blocking the BK channels with paxilline. 17β-Estradiol (100 nM) had no effects on L-type voltage-gated Ca2+ channel currents recorded under perforated patch-clamp conditions. This study reveals a new regulatory mechanism in the urinary bladder whereby BK channels are directly activated by 17β-estradiol to reduce UBSM cell excitability.",
author = "Aaron Provence and Hristov, {Kiril L.} and Parajuli, {Shankar P.} and Georgi Petkov",
year = "2015",
month = "11",
day = "4",
doi = "10.1371/journal.pone.0141950",
language = "English (US)",
volume = "10",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "11",

}

TY - JOUR

T1 - Regulation of Guinea Pig detrusor smooth muscle excitability by 17β-estradiol

T2 - The role of the large conductance voltage- and Ca2+-activated K+ channels

AU - Provence, Aaron

AU - Hristov, Kiril L.

AU - Parajuli, Shankar P.

AU - Petkov, Georgi

PY - 2015/11/4

Y1 - 2015/11/4

N2 - Estrogen replacement therapies have been suggested to be beneficial in alleviating symptoms of overactive bladder. However, the precise regulatory mechanisms of estrogen in urinary bladder smooth muscle (UBSM) at the cellular level remain unknown. Large conductance voltage- and Ca2+-activated K+ (BK) channels, which are key regulators of UBSM function, are suggested to be non-genomic targets of estrogens. This study provides an electrophysiological investigation into the role of UBSM BK channels as direct targets for 17β-estradiol, the principle estrogen in human circulation. Single BK channel recordings on inside-out excised membrane patches and perforated whole cell patch-clamp were applied in combination with the BK channel selective inhibitor paxilline to elucidate the mechanism of regulation of BK channel activity by 17β-estradiol in freshly-isolated Guinea pig UBSM cells. 17β-Estradiol (100 nM) significantly increased the amplitude of depolarizationinduced whole cell steady-state BK currents and the frequency of spontaneous transient BK currents in freshly-isolated UBSM cells. The increase in whole cell BK currents by 17β- estradiol was eliminated upon blocking BK channels with paxilline. 17β-Estradiol (100 nM) significantly increased (∼3-fold) the single BK channel open probability, indicating direct 17β-estradiol-BK channel interactions. 17β-Estradiol (100 nM) caused a significant hyperpolarization of the membrane potential of UBSM cells, and this hyperpolarization was reversed by blocking the BK channels with paxilline. 17β-Estradiol (100 nM) had no effects on L-type voltage-gated Ca2+ channel currents recorded under perforated patch-clamp conditions. This study reveals a new regulatory mechanism in the urinary bladder whereby BK channels are directly activated by 17β-estradiol to reduce UBSM cell excitability.

AB - Estrogen replacement therapies have been suggested to be beneficial in alleviating symptoms of overactive bladder. However, the precise regulatory mechanisms of estrogen in urinary bladder smooth muscle (UBSM) at the cellular level remain unknown. Large conductance voltage- and Ca2+-activated K+ (BK) channels, which are key regulators of UBSM function, are suggested to be non-genomic targets of estrogens. This study provides an electrophysiological investigation into the role of UBSM BK channels as direct targets for 17β-estradiol, the principle estrogen in human circulation. Single BK channel recordings on inside-out excised membrane patches and perforated whole cell patch-clamp were applied in combination with the BK channel selective inhibitor paxilline to elucidate the mechanism of regulation of BK channel activity by 17β-estradiol in freshly-isolated Guinea pig UBSM cells. 17β-Estradiol (100 nM) significantly increased the amplitude of depolarizationinduced whole cell steady-state BK currents and the frequency of spontaneous transient BK currents in freshly-isolated UBSM cells. The increase in whole cell BK currents by 17β- estradiol was eliminated upon blocking BK channels with paxilline. 17β-Estradiol (100 nM) significantly increased (∼3-fold) the single BK channel open probability, indicating direct 17β-estradiol-BK channel interactions. 17β-Estradiol (100 nM) caused a significant hyperpolarization of the membrane potential of UBSM cells, and this hyperpolarization was reversed by blocking the BK channels with paxilline. 17β-Estradiol (100 nM) had no effects on L-type voltage-gated Ca2+ channel currents recorded under perforated patch-clamp conditions. This study reveals a new regulatory mechanism in the urinary bladder whereby BK channels are directly activated by 17β-estradiol to reduce UBSM cell excitability.

UR - http://www.scopus.com/inward/record.url?scp=84951208606&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84951208606&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0141950

DO - 10.1371/journal.pone.0141950

M3 - Article

VL - 10

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 11

M1 - 141950

ER -