Neurogenic Detrusor Overactivity Is Associated with Decreased Expression and Function of the Large Conductance Voltage- and Ca2+-Activated K+ Channels

Kiril L. Hristov, Serge A.Y. Afeli, Shankar P. Parajuli, Qiuping Cheng, Eric S. Rovner, Georgi Petkov

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Patients suffering from a variety of neurological diseases such as spinal cord injury, Parkinson's disease, and multiple sclerosis often develop neurogenic detrusor overactivity (NDO), which currently lacks a universally effective therapy. Here, we tested the hypothesis that NDO is associated with changes in detrusor smooth muscle (DSM) large conductance Ca2+-activated K+ (BK) channel expression and function. DSM tissue samples from 33 patients were obtained during open bladder surgeries. NDO patients were clinically characterized preoperatively with pressure-flow urodynamics demonstrating detrusor overactivity, in the setting of a clinically relevant neurological condition. Control patients did not have overactive bladder and did not have a clinically relevant neurological disease. We conducted quantitative polymerase chain reactions (qPCR), perforated patch-clamp electrophysiology on freshly-isolated DSM cells, and functional studies on DSM contractility. qPCR experiments revealed that DSM samples from NDO patients showed decreased BK channel mRNA expression in comparison to controls. Patch-clamp experiments demonstrated reduced whole cell and transient BK currents (TBKCs) in freshly-isolated DSM cells from NDO patients. Functional studies on DSM contractility showed that spontaneous phasic contractions had a decreased sensitivity to iberiotoxin, a selective BK channel inhibitor, in DSM strips isolated from NDO patients. These results reveal the novel finding that NDO is associated with decreased DSM BK channel expression and function leading to increased DSM excitability and contractility. BK channel openers or BK channel gene transfer could be an alternative strategy to control NDO. Future clinical trials are needed to evaluate the value of BK channel opening drugs or gene therapies for NDO treatment and to identify any possible adverse effects.

Original languageEnglish (US)
Article numbere68052
JournalPloS one
Volume8
Issue number7
DOIs
StatePublished - Jul 5 2013

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Calcium-Activated Potassium Channels
Large-Conductance Calcium-Activated Potassium Channels
potassium channels
smooth muscle
Smooth Muscle
Muscle
calcium
Electric potential
muscle strength
Polymerase chain reaction
Smooth Muscle Myocytes
Clamping devices
bladder
myocytes
quantitative polymerase chain reaction
Overactive Urinary Bladder
Polymerase Chain Reaction
Urodynamics
Electrophysiology
Gene transfer

All Science Journal Classification (ASJC) codes

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

Cite this

Neurogenic Detrusor Overactivity Is Associated with Decreased Expression and Function of the Large Conductance Voltage- and Ca2+-Activated K+ Channels. / Hristov, Kiril L.; Afeli, Serge A.Y.; Parajuli, Shankar P.; Cheng, Qiuping; Rovner, Eric S.; Petkov, Georgi.

In: PloS one, Vol. 8, No. 7, e68052, 05.07.2013.

Research output: Contribution to journalArticle

Hristov, Kiril L. ; Afeli, Serge A.Y. ; Parajuli, Shankar P. ; Cheng, Qiuping ; Rovner, Eric S. ; Petkov, Georgi. / Neurogenic Detrusor Overactivity Is Associated with Decreased Expression and Function of the Large Conductance Voltage- and Ca2+-Activated K+ Channels. In: PloS one. 2013 ; Vol. 8, No. 7.
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