Testosterone decreases urinary bladder smooth muscle excitability via novel signaling mechanism involving direct activation of the BK channels

Kiril L. Hristov, Shankar P. Parajuli, Aaron Provence, Georgi Petkov

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

In addition to improving sexual function, testosterone has been reported to have beneficial effects in ameliorating lower urinary tract symptoms by increasing bladder capacity and compliance, while decreasing bladder pressure. However, the cellular mechanisms by which testosterone regulates detrusor smooth muscle (DSM) excitability have not been elucidated. Here, we used amphotericin-B perforated whole cell patch-clamp and single channel recordings on inside-out excised membrane patches to investigate the regulatory role of testosterone in guinea pig DSM excitability. Testosterone (100 nM) significantly increased the depolarization-induced whole cell outward currents in DSM cells. The selective pharmacological inhibition of the largeconductance voltage- and Ca2+-activated K+ (BK) channels with paxilline (1 μM) completely abolished this stimulatory effect of testosterone, suggesting a mechanism involving BK channels. At a holding potential of −20 mV, DSM cells exhibited transient BK currents (TBKCs). Testosterone (100 nM) significantly increased TBKC activity in DSM cells. In current-clamp mode, testosterone (100 nM) significantly hyperpolarized the DSM cell resting membrane potential and increased spontaneous transient hyperpolarizations. Testosterone (100 nM) rapidly increased the single BK channel open probability in inside-out excised membrane patches from DSM cells, clearly suggesting a direct BK channel activation via a nongenomic mechanism. Live-cell Ca2+ imaging showed that testosterone (100 nM) caused a decrease in global intracellular Ca2+ concentration, consistent with testosterone-induced membrane hyperpolarization. In conclusion, the data provide compelling mechanistic evidence that under physiological conditions, testosterone at nanomolar concentrations directly activates BK channels in DSM cells, independent from genomic testosterone receptors, and thus regulates DSM excitability.

Original languageEnglish (US)
Pages (from-to)F1253-F1259
JournalAmerican Journal of Physiology - Renal Physiology
Volume311
Issue number6
DOIs
StatePublished - Dec 1 2016

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Large-Conductance Calcium-Activated Potassium Channels
Smooth Muscle
Testosterone
Urinary Bladder
Smooth Muscle Myocytes
Membranes
Calcium-Activated Potassium Channels
Lower Urinary Tract Symptoms
Androgen Receptors
Amphotericin B
Membrane Potentials
Compliance
Guinea Pigs

All Science Journal Classification (ASJC) codes

  • Physiology
  • Urology

Cite this

Testosterone decreases urinary bladder smooth muscle excitability via novel signaling mechanism involving direct activation of the BK channels. / Hristov, Kiril L.; Parajuli, Shankar P.; Provence, Aaron; Petkov, Georgi.

In: American Journal of Physiology - Renal Physiology, Vol. 311, No. 6, 01.12.2016, p. F1253-F1259.

Research output: Contribution to journalArticle

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