Large-conductance voltage-and Ca 2+-activated K + channels regulate human

Detrusor Smooth Muscle Function, Kiril L. Hristov, Muyan Chen, Whitney F. Kellett, Eric S. Rovner, Georgi Petkov

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

The large-conductance voltageand Ca2 +-activated K + (BK) channel is expressed in many smooth muscle types, but its role in human detrusor smooth muscle (DSM) is unclear. With a multidisciplinary approach spanning channel molecules, single-channel activity, freshly isolated human DSM cells, intact DSM preparations, and the BK channel specific inhibitor iberiotoxin, we elucidated human DSM BK channel function and regulation. Native human DSM tissues were obtained during open surgeries from patients with no preoperative history of overactive bladder. RT-PCR experiments on single human DSM cells showed mRNA expression of BK channel α-, β 1-, and β 4-subunits. Western blot and immunocytochemistry confirmed BK channel α, β 1, and β 4 protein expression. Native human BK channel properties were described using the perforated whole cell configuration of the patchclamp technique. In freshly isolated human DSM cells, BK channel blockade with iberiotoxin inhibited a significant portion of the total voltage step-induced whole cell K + current. From single BK channel recordings, human BK channel conductance was calculated to be 136 pS. Voltage-dependent iberiotoxin- and ryanodine-sensitive transient BK currents were identified in human DSM cells. In current-clamp mode, iberiotoxin inhibited the hyperpolarizing membrane potential transients and depolarized the cell resting membrane potential. Isometric DSM tension recordings revealed that BK channels principally control the contractions of isolated human DSM strips. Collectively, our results indicate that BK channels are fundamental regulators of DSM excitability and contractility and may represent new targets for pharmacological or genetic control of urinary bladder function in humans.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume301
Issue number4
DOIs
StatePublished - Oct 1 2011

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Large-Conductance Calcium-Activated Potassium Channels
Smooth Muscle
Smooth Muscle Myocytes
Population Groups
Membrane Potentials
Calcium-Activated Potassium Channels
Overactive Urinary Bladder
Ryanodine
Muscle Tonus
Urinary Bladder
Western Blotting

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cell Biology

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Large-conductance voltage-and Ca 2+-activated K + channels regulate human. / Function, Detrusor Smooth Muscle; Hristov, Kiril L.; Chen, Muyan; Kellett, Whitney F.; Rovner, Eric S.; Petkov, Georgi.

In: American Journal of Physiology - Cell Physiology, Vol. 301, No. 4, 01.10.2011.

Research output: Contribution to journalArticle

Function, Detrusor Smooth Muscle ; Hristov, Kiril L. ; Chen, Muyan ; Kellett, Whitney F. ; Rovner, Eric S. ; Petkov, Georgi. / Large-conductance voltage-and Ca 2+-activated K + channels regulate human. In: American Journal of Physiology - Cell Physiology. 2011 ; Vol. 301, No. 4.
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