Inositol trisphosphate-dependent Ca2+ stores and mitochondria modulate slow wave activity arising from the smooth muscle cells of the guinea pig prostate gland |
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Authors: | Betty Exintaris Dan-Thanh T Nguyen Michelle Lam Richard J Lang |
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Institution: | 1Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, Parkville Victoria 3052 Australia;2Department of Physiology, Monash University, Clayton Victoria 3800 Australia |
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Abstract: | Background and purposeChanges 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 Ca2+ compartments in regulating slow wave activity in the guinea pig prostate.Experimental approachStandard intracellular membrane potential recording techniques were used.Key resultsThe majority (89%) of impaled cells displayed ‘slow wave’ activity. Cyclopiazonic acid (10 µmol·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 Ca2+ release with 2-aminoethoxy-diphenylborate (60 µmol·L?1) or Xestospongin C (3 µmol·L?1) or inhibiting phospholipase C and IP3 formation using {"type":"entrez-nucleotide","attrs":{"text":"U73122","term_id":"4098075","term_text":"U73122"}}U73122 (5 µmol·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 µmol·L?1), carbonyl cyanide m-chlorophenylhydrazone (1–3 µmol·L?1) or rotenone (10 µmol·L?1), depolarized the membrane (8–10 mV) before abolishing electrical activity.Conclusion and implicationsThese results suggest that slow wave activity was dependent on the cyclical release of Ca2+ 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. |
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Keywords: | cyclopiazonic acid IP3-dependent Ca2+ stores pacemaker activity prostate slow waves smooth muscle |
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