SK channel-selective opening by SKA-31 induces hyperpolarization and decreases contractility in human urinary bladder smooth muscle

Rupal P. Soder, Shankar P. Parajuli, Kiril L. Hristov, Eric S. Rovner, Georgi Petkov

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Overactive bladder (OAB) is often associated with increased involuntary detrusor smooth muscle (DSM) contractions during the bladder- filling phase. To develop novel therapies for OAB, it is critical to better understand the mechanisms that control DSM excitability and contractility. Recent studies showed that small-conductance Ca2+- activated K (SK) channels, SK3 channels, in particular, regulate human DSM function. However, the concept that SK channel-selective pharmacological activation can decrease the excitability and contractility directly in human DSM needs further exploration. Here, we studied the effect of the novel and potent SK channel activator, SKA-31 (or naphtho [1,2-d]thiazol-2-ylamine), on human DSM excitability and contractility at the cellular and tissue level. We used isometric tension recordings on human DSM-isolated strips and the perforated patch-clamp technique on freshly isolated native human DSM cells. SKA-31 significantly decreased spontaneous phasic contractions of DSM-isolated strips. In the presence of the SK channel blocker, apamin, the inhibitory effects of SKA-31 on the DSM spontaneous phasic contractions were significantly reduced. SKA-31 decreased the carbachol- and KCl-induced contractions in human DSM strips. Electrical field stimulation-induced contractions were significantly attenuated in the presence of SKA-31 at all stimulation frequencies (0.5-50 Hz). SKA-31 hyperpolarized the resting membrane potential of human DSM cells. Apamin abolished the hyperpolarizing effect of SKA-31, indicating the involvement of SK channel activation. These results support the concept that pharmacological activation of SK channels with selective openers may represent an attractive new pharmacological approach for decreasing DSM excitability and contractility, thus controlling OAB.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume304
Issue number2
DOIs
StatePublished - Jan 15 2013

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Smooth Muscle
Urinary Bladder
Overactive Urinary Bladder
Apamin
Smooth Muscle Myocytes
naphtho(1,2-d)thiazol-2-ylamine
Pharmacology
Calcium-Activated Potassium Channels
Carbachol
Patch-Clamp Techniques
Muscle Contraction
Population Groups
Membrane Potentials
Electric Stimulation

All Science Journal Classification (ASJC) codes

  • Physiology
  • Physiology (medical)

Cite this

SK channel-selective opening by SKA-31 induces hyperpolarization and decreases contractility in human urinary bladder smooth muscle. / Soder, Rupal P.; Parajuli, Shankar P.; Hristov, Kiril L.; Rovner, Eric S.; Petkov, Georgi.

In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 304, No. 2, 15.01.2013.

Research output: Contribution to journalArticle

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