Inositol trisphosphate-dependent Ca stores and mitochondria modulate slow wave activity arising from the smooth muscle cells of the guinea pig prostate gland.

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 micromol.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 (IP(3)R)-mediated Ca(2+) release with 2-aminoethoxy-diphenylborate (60 micromol.L(-1)) or Xestospongin C (3 micromol.L(-1)) or inhibiting phospholipase C and IP(3) formation using U73122 (5 micromol.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 micromol.L(-1)), carbonyl cyanide m-chlorophenylhydrazone (1-3 micromol.L(-1)) or rotenone (10 micromol.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 IP(3)-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.