Inositol trisphosphate‐dependent Ca²⁺ stores and mitochondria modulate slow wave activity arising from the smooth muscle cells of the guinea pig prostate gland

Abstract

Background and purpose: Changes in smooth muscle tone of the prostate gland are involved in aetiology of symptomatic prostatic hyperplasia, however the control mechanisms of prostatic smooth muscle are not well understood. Here, we have examined the role of internal Ca 2+ compartments in regulating slow wave activity in the guinea pig prostate. Experimental approach: Standard intracellular membrane potential recording techniques were used. Key results: The majority (89%) of impaled cells displayed 'slow wave' activity. Cyclopiazonic acid (10 mmol·L -1 ) transiently depolarized (3-9 mV) the membrane potential of the prostatic stroma and transiently increased slow wave frequency. Thereafter, slow wave frequency slowly decreased over 20-30 min. Ryanodine transiently increased slow wave frequency, although after 30 min exposure slow wave frequency and time course returned to near control values. Caffeine (1 mmol·L -1 ) reduced slow wave frequency, accompanied by membrane depolarization of about 8 mV. Blockade of inositol trisphosphate receptor (IP3R)-mediated Ca 2+ release with 2-aminoethoxy-diphenylborate (60 mmol·L -1 ) or Xestospongin C (3 mmol·L -1 ) or inhibiting phospholipase C and IP3 formation using U73122 (5 mmol·L -1 ) or neomycin (1 and 4 mmol·L -1 ) reduced slow wave frequency, amplitude and duration. The mitochondrial uncouplers, p-trifluoromethoxy carbonyl cyanide phenyl hydrazone (1-10 mmol·L -1 ), carbonyl cyanide m-chlorophenylhydrazone (1-3 mmol·L -1 ) or rotenone (10 mmol·L -1 ), depolarized the membrane (8-10 mV) before abolishing electrical activity. Conclusion and implications:These results suggest that slow wave activity was dependent on the cyclical release of Ca 2+ from IP3-controlled internal stores and mitochondria. This implies that intracellular compartments were essential in the initiation and/or maintenance of the regenerative contractile activity in the guinea pig prostate gland.

Synchronization of Ca2+ oscillations: a coupled oscillator‐based mechanism in smooth muscle

“…Slow waves are rhythmic electrical depolarizations that control the mechanical activity of many smooth muscles [1,11–13] (Fig. 1).…”

Oxytocin depolarizes mitochondria in isolated myometrial cells

“…the mitochondrial membrane potential, ψ m ), which has a direct impact on Ca 2+ buffering. Mitochondria play an important role in a variety of smooth muscle organs, including the gallbladder (Balemba et al 2008), the prostate (Exintaris et al 2009) and the gut (Sanders et al 2006), and have a modulatory role in spontaneous uterine contractions (Gravina et al 2010).…”

Tamsulosin modulates, but does not abolish the spontaneous activity in the guinea pig prostate gland

“…Tamsulosin binding at α 1 ‐adrenoceptors results in an agonist‐independent inhibition of inositol phosphate . Initiation and maintenance of spontaneous electrical activity in the guinea pig prostate gland is modulated by inositol triphosphate‐dependent Ca 2+ release from intracellular stores . These mechanisms play an important role in the generation of spontaneous electrical activity that underlies spontaneous contractile activity.…”