Small-conductance, Ca2+-activated K+ channel 2 is the key functional component of SK channels in mouse urinary bladder

K. S. Thorneloe, A. M. Knorn, P. E. Doetsch, E. S R Lashinger, A. X. Liu, C. T. Bond, John Adelman, M. T. Nelson

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Small-conductance Ca2+-activated K+ (SK) channels play an important role in regulating the frequency and in shaping urinary bladder smooth muscle (UBSM) action potentials, thereby modulating contractility. Here we investigated a role for the SK2 member of the SK family (SK1-3) utilizing: 1) mice expressing β-galactosidase (β-gal) under the direction of the SK2 promoter (SK2 β-gal mice) to localize SK2 expression and 2) mice lacking SK2 gene expression (SK2-/- mice) to assess SK2 function. In SK2 β-gal mice, UBSM staining was observed, but staining was undetected in the urothelium. Consistent with this, urothelial SK2 mRNA was determined to be 4% of that in UBSM. Spontaneous phasic contractions in wild-type (SK2+/+) UBSM strips were potentiated (259% of control) by the selective SK channel blocker apamin (EC50 = 0.16 nM), whereas phasic contractions of SK2-/- strips were unaffected. Nerve-mediated contractions of SK2+/+ UBSM strips were also increased by apamin, an effect absent in SK2-/- strips. Apamin increased the sensitivity of SK2+/+ UBSM strips to electrical field stimulation, since pretreatment with apamin decreased the frequency required to reach a 50% maximal contraction (vehicle, 21 ± 4 Hz, n = 6; apamin, 12 ± 2 Hz, n = 7; P <0.05). In contrast, the sensitivity of SK2-/- UBSM strips was unaffected by apamin. Here we provide novel insight into the molecular basis of SK channels in the urinary bladder, demonstrating that the SK2 gene is expressed in the bladder and that it is essential for the ability of SK channels to regulate UBSM contractility.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume294
Issue number5
DOIs
StatePublished - May 2008

Fingerprint

Calcium-Activated Potassium Channels
Urinary Bladder
Apamin
Smooth Muscle
Galactosidases
Staining and Labeling
Urothelium
Aptitude
Electric Stimulation
Action Potentials
Gene Expression

Keywords

  • Apamin
  • Bladder
  • Contractility
  • Small-conductance calcium-activated potassium channel

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Small-conductance, Ca2+-activated K+ channel 2 is the key functional component of SK channels in mouse urinary bladder. / Thorneloe, K. S.; Knorn, A. M.; Doetsch, P. E.; Lashinger, E. S R; Liu, A. X.; Bond, C. T.; Adelman, John; Nelson, M. T.

In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 294, No. 5, 05.2008.

Research output: Contribution to journalArticle

Thorneloe, K. S. ; Knorn, A. M. ; Doetsch, P. E. ; Lashinger, E. S R ; Liu, A. X. ; Bond, C. T. ; Adelman, John ; Nelson, M. T. / Small-conductance, Ca2+-activated K+ channel 2 is the key functional component of SK channels in mouse urinary bladder. In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology. 2008 ; Vol. 294, No. 5.
@article{5882397a4499485d980e10dd261db2c0,
title = "Small-conductance, Ca2+-activated K+ channel 2 is the key functional component of SK channels in mouse urinary bladder",
abstract = "Small-conductance Ca2+-activated K+ (SK) channels play an important role in regulating the frequency and in shaping urinary bladder smooth muscle (UBSM) action potentials, thereby modulating contractility. Here we investigated a role for the SK2 member of the SK family (SK1-3) utilizing: 1) mice expressing β-galactosidase (β-gal) under the direction of the SK2 promoter (SK2 β-gal mice) to localize SK2 expression and 2) mice lacking SK2 gene expression (SK2-/- mice) to assess SK2 function. In SK2 β-gal mice, UBSM staining was observed, but staining was undetected in the urothelium. Consistent with this, urothelial SK2 mRNA was determined to be 4{\%} of that in UBSM. Spontaneous phasic contractions in wild-type (SK2+/+) UBSM strips were potentiated (259{\%} of control) by the selective SK channel blocker apamin (EC50 = 0.16 nM), whereas phasic contractions of SK2-/- strips were unaffected. Nerve-mediated contractions of SK2+/+ UBSM strips were also increased by apamin, an effect absent in SK2-/- strips. Apamin increased the sensitivity of SK2+/+ UBSM strips to electrical field stimulation, since pretreatment with apamin decreased the frequency required to reach a 50{\%} maximal contraction (vehicle, 21 ± 4 Hz, n = 6; apamin, 12 ± 2 Hz, n = 7; P <0.05). In contrast, the sensitivity of SK2-/- UBSM strips was unaffected by apamin. Here we provide novel insight into the molecular basis of SK channels in the urinary bladder, demonstrating that the SK2 gene is expressed in the bladder and that it is essential for the ability of SK channels to regulate UBSM contractility.",
keywords = "Apamin, Bladder, Contractility, Small-conductance calcium-activated potassium channel",
author = "Thorneloe, {K. S.} and Knorn, {A. M.} and Doetsch, {P. E.} and Lashinger, {E. S R} and Liu, {A. X.} and Bond, {C. T.} and John Adelman and Nelson, {M. T.}",
year = "2008",
month = "5",
doi = "10.1152/ajpregu.00840.2006",
language = "English (US)",
volume = "294",
journal = "American Journal of Physiology - Renal Fluid and Electrolyte Physiology",
issn = "1931-857X",
publisher = "American Physiological Society",
number = "5",

}

TY - JOUR

T1 - Small-conductance, Ca2+-activated K+ channel 2 is the key functional component of SK channels in mouse urinary bladder

AU - Thorneloe, K. S.

AU - Knorn, A. M.

AU - Doetsch, P. E.

AU - Lashinger, E. S R

AU - Liu, A. X.

AU - Bond, C. T.

AU - Adelman, John

AU - Nelson, M. T.

PY - 2008/5

Y1 - 2008/5

N2 - Small-conductance Ca2+-activated K+ (SK) channels play an important role in regulating the frequency and in shaping urinary bladder smooth muscle (UBSM) action potentials, thereby modulating contractility. Here we investigated a role for the SK2 member of the SK family (SK1-3) utilizing: 1) mice expressing β-galactosidase (β-gal) under the direction of the SK2 promoter (SK2 β-gal mice) to localize SK2 expression and 2) mice lacking SK2 gene expression (SK2-/- mice) to assess SK2 function. In SK2 β-gal mice, UBSM staining was observed, but staining was undetected in the urothelium. Consistent with this, urothelial SK2 mRNA was determined to be 4% of that in UBSM. Spontaneous phasic contractions in wild-type (SK2+/+) UBSM strips were potentiated (259% of control) by the selective SK channel blocker apamin (EC50 = 0.16 nM), whereas phasic contractions of SK2-/- strips were unaffected. Nerve-mediated contractions of SK2+/+ UBSM strips were also increased by apamin, an effect absent in SK2-/- strips. Apamin increased the sensitivity of SK2+/+ UBSM strips to electrical field stimulation, since pretreatment with apamin decreased the frequency required to reach a 50% maximal contraction (vehicle, 21 ± 4 Hz, n = 6; apamin, 12 ± 2 Hz, n = 7; P <0.05). In contrast, the sensitivity of SK2-/- UBSM strips was unaffected by apamin. Here we provide novel insight into the molecular basis of SK channels in the urinary bladder, demonstrating that the SK2 gene is expressed in the bladder and that it is essential for the ability of SK channels to regulate UBSM contractility.

AB - Small-conductance Ca2+-activated K+ (SK) channels play an important role in regulating the frequency and in shaping urinary bladder smooth muscle (UBSM) action potentials, thereby modulating contractility. Here we investigated a role for the SK2 member of the SK family (SK1-3) utilizing: 1) mice expressing β-galactosidase (β-gal) under the direction of the SK2 promoter (SK2 β-gal mice) to localize SK2 expression and 2) mice lacking SK2 gene expression (SK2-/- mice) to assess SK2 function. In SK2 β-gal mice, UBSM staining was observed, but staining was undetected in the urothelium. Consistent with this, urothelial SK2 mRNA was determined to be 4% of that in UBSM. Spontaneous phasic contractions in wild-type (SK2+/+) UBSM strips were potentiated (259% of control) by the selective SK channel blocker apamin (EC50 = 0.16 nM), whereas phasic contractions of SK2-/- strips were unaffected. Nerve-mediated contractions of SK2+/+ UBSM strips were also increased by apamin, an effect absent in SK2-/- strips. Apamin increased the sensitivity of SK2+/+ UBSM strips to electrical field stimulation, since pretreatment with apamin decreased the frequency required to reach a 50% maximal contraction (vehicle, 21 ± 4 Hz, n = 6; apamin, 12 ± 2 Hz, n = 7; P <0.05). In contrast, the sensitivity of SK2-/- UBSM strips was unaffected by apamin. Here we provide novel insight into the molecular basis of SK channels in the urinary bladder, demonstrating that the SK2 gene is expressed in the bladder and that it is essential for the ability of SK channels to regulate UBSM contractility.

KW - Apamin

KW - Bladder

KW - Contractility

KW - Small-conductance calcium-activated potassium channel

UR - http://www.scopus.com/inward/record.url?scp=45549104511&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=45549104511&partnerID=8YFLogxK

U2 - 10.1152/ajpregu.00840.2006

DO - 10.1152/ajpregu.00840.2006

M3 - Article

VL - 294

JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

SN - 1931-857X

IS - 5

ER -