β1-subunit of the Ca2+-activated K+ channel regulates contractile activity of mouse urinary bladder smooth muscle

Georgi Petkov, Adrian D. Bonev, Thomas J. Heppner, Robert Brenner, Richard W. Aldrich, Mark T. Nelson

Research output: Contribution to journalArticle

125 Citations (Scopus)

Abstract

1. The large-conductance calcium-activated potassium (BK) channel plays an important role in controlling membrane potential and contractility of urinary bladder smooth muscle (UBSM). These channels are composed of a pore-forming α-subunit and an accessory, smooth muscle-specific, β1-subunit. 2. Our aim was to determine the functional role of the β1-subunit of the BK channel in controlling the contractions of UBSM by using BK channel β1-subunit 'knock-out' (KO) mice. 3. The β-galactosidase reporter (lacZ gene) was targeted to the β1 locus, which provided the opportunity to examine the expression of the β1-subunit in UBSM. Based on this approach, the β1-subunit is highly expressed in UBSM. 4. BK channels lacking β1-subunits have reduced activity, consistent with a shift in BK channel voltage/Ca2+ sensitivity. 5. Iberiotoxin, an inhibitor of BK channels, increased the amplitude and decreased the frequency of phasic contractions of UBSM strips from control mice. 6. The effects of the β1-subunit deletion on contractions were similar to the effect of iberiotoxin on control mice. The UBSM strips from β1-subunit KO mice had elevated phasic contraction amplitude and decreased frequency when compared to control UBSM strips. 7. Iberiotoxin increased the amplitude and frequency of phasic contractions, and UBSM tone of UBSM strips from β1-subunit KO mice, suggesting that BK channels still regulate contractions in the absence of the β1-subunit. 8. The results indicate that the β1-subunit, by modulating BK channel activity, plays a significant role in the regulation of phasic contractions of the urinary bladder.

Original languageEnglish (US)
Pages (from-to)443-452
Number of pages10
JournalJournal of Physiology
Volume537
Issue number2
DOIs
StatePublished - Dec 1 2001

Fingerprint

Calcium-Activated Potassium Channels
Large-Conductance Calcium-Activated Potassium Channels
Smooth Muscle
Urinary Bladder
Knockout Mice
Galactosidases
Lac Operon
Reporter Genes
Membrane Potentials

All Science Journal Classification (ASJC) codes

  • Physiology

Cite this

β1-subunit of the Ca2+-activated K+ channel regulates contractile activity of mouse urinary bladder smooth muscle. / Petkov, Georgi; Bonev, Adrian D.; Heppner, Thomas J.; Brenner, Robert; Aldrich, Richard W.; Nelson, Mark T.

In: Journal of Physiology, Vol. 537, No. 2, 01.12.2001, p. 443-452.

Research output: Contribution to journalArticle

Petkov, Georgi ; Bonev, Adrian D. ; Heppner, Thomas J. ; Brenner, Robert ; Aldrich, Richard W. ; Nelson, Mark T. / β1-subunit of the Ca2+-activated K+ channel regulates contractile activity of mouse urinary bladder smooth muscle. In: Journal of Physiology. 2001 ; Vol. 537, No. 2. pp. 443-452.
@article{fd4e6d9bebb74a6f9b51603c526f72e6,
title = "β1-subunit of the Ca2+-activated K+ channel regulates contractile activity of mouse urinary bladder smooth muscle",
abstract = "1. The large-conductance calcium-activated potassium (BK) channel plays an important role in controlling membrane potential and contractility of urinary bladder smooth muscle (UBSM). These channels are composed of a pore-forming α-subunit and an accessory, smooth muscle-specific, β1-subunit. 2. Our aim was to determine the functional role of the β1-subunit of the BK channel in controlling the contractions of UBSM by using BK channel β1-subunit 'knock-out' (KO) mice. 3. The β-galactosidase reporter (lacZ gene) was targeted to the β1 locus, which provided the opportunity to examine the expression of the β1-subunit in UBSM. Based on this approach, the β1-subunit is highly expressed in UBSM. 4. BK channels lacking β1-subunits have reduced activity, consistent with a shift in BK channel voltage/Ca2+ sensitivity. 5. Iberiotoxin, an inhibitor of BK channels, increased the amplitude and decreased the frequency of phasic contractions of UBSM strips from control mice. 6. The effects of the β1-subunit deletion on contractions were similar to the effect of iberiotoxin on control mice. The UBSM strips from β1-subunit KO mice had elevated phasic contraction amplitude and decreased frequency when compared to control UBSM strips. 7. Iberiotoxin increased the amplitude and frequency of phasic contractions, and UBSM tone of UBSM strips from β1-subunit KO mice, suggesting that BK channels still regulate contractions in the absence of the β1-subunit. 8. The results indicate that the β1-subunit, by modulating BK channel activity, plays a significant role in the regulation of phasic contractions of the urinary bladder.",
author = "Georgi Petkov and Bonev, {Adrian D.} and Heppner, {Thomas J.} and Robert Brenner and Aldrich, {Richard W.} and Nelson, {Mark T.}",
year = "2001",
month = "12",
day = "1",
doi = "10.1111/j.1469-7793.2001.00443.x",
language = "English (US)",
volume = "537",
pages = "443--452",
journal = "Journal of Physiology",
issn = "0022-3751",
publisher = "Wiley-Blackwell",
number = "2",

}

TY - JOUR

T1 - β1-subunit of the Ca2+-activated K+ channel regulates contractile activity of mouse urinary bladder smooth muscle

AU - Petkov, Georgi

AU - Bonev, Adrian D.

AU - Heppner, Thomas J.

AU - Brenner, Robert

AU - Aldrich, Richard W.

AU - Nelson, Mark T.

PY - 2001/12/1

Y1 - 2001/12/1

N2 - 1. The large-conductance calcium-activated potassium (BK) channel plays an important role in controlling membrane potential and contractility of urinary bladder smooth muscle (UBSM). These channels are composed of a pore-forming α-subunit and an accessory, smooth muscle-specific, β1-subunit. 2. Our aim was to determine the functional role of the β1-subunit of the BK channel in controlling the contractions of UBSM by using BK channel β1-subunit 'knock-out' (KO) mice. 3. The β-galactosidase reporter (lacZ gene) was targeted to the β1 locus, which provided the opportunity to examine the expression of the β1-subunit in UBSM. Based on this approach, the β1-subunit is highly expressed in UBSM. 4. BK channels lacking β1-subunits have reduced activity, consistent with a shift in BK channel voltage/Ca2+ sensitivity. 5. Iberiotoxin, an inhibitor of BK channels, increased the amplitude and decreased the frequency of phasic contractions of UBSM strips from control mice. 6. The effects of the β1-subunit deletion on contractions were similar to the effect of iberiotoxin on control mice. The UBSM strips from β1-subunit KO mice had elevated phasic contraction amplitude and decreased frequency when compared to control UBSM strips. 7. Iberiotoxin increased the amplitude and frequency of phasic contractions, and UBSM tone of UBSM strips from β1-subunit KO mice, suggesting that BK channels still regulate contractions in the absence of the β1-subunit. 8. The results indicate that the β1-subunit, by modulating BK channel activity, plays a significant role in the regulation of phasic contractions of the urinary bladder.

AB - 1. The large-conductance calcium-activated potassium (BK) channel plays an important role in controlling membrane potential and contractility of urinary bladder smooth muscle (UBSM). These channels are composed of a pore-forming α-subunit and an accessory, smooth muscle-specific, β1-subunit. 2. Our aim was to determine the functional role of the β1-subunit of the BK channel in controlling the contractions of UBSM by using BK channel β1-subunit 'knock-out' (KO) mice. 3. The β-galactosidase reporter (lacZ gene) was targeted to the β1 locus, which provided the opportunity to examine the expression of the β1-subunit in UBSM. Based on this approach, the β1-subunit is highly expressed in UBSM. 4. BK channels lacking β1-subunits have reduced activity, consistent with a shift in BK channel voltage/Ca2+ sensitivity. 5. Iberiotoxin, an inhibitor of BK channels, increased the amplitude and decreased the frequency of phasic contractions of UBSM strips from control mice. 6. The effects of the β1-subunit deletion on contractions were similar to the effect of iberiotoxin on control mice. The UBSM strips from β1-subunit KO mice had elevated phasic contraction amplitude and decreased frequency when compared to control UBSM strips. 7. Iberiotoxin increased the amplitude and frequency of phasic contractions, and UBSM tone of UBSM strips from β1-subunit KO mice, suggesting that BK channels still regulate contractions in the absence of the β1-subunit. 8. The results indicate that the β1-subunit, by modulating BK channel activity, plays a significant role in the regulation of phasic contractions of the urinary bladder.

UR - http://www.scopus.com/inward/record.url?scp=0035529041&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035529041&partnerID=8YFLogxK

U2 - 10.1111/j.1469-7793.2001.00443.x

DO - 10.1111/j.1469-7793.2001.00443.x

M3 - Article

VL - 537

SP - 443

EP - 452

JO - Journal of Physiology

JF - Journal of Physiology

SN - 0022-3751

IS - 2

ER -