ROLE OF CALCIUM STORES IN THE GENERATION OF SPONTANEOUS ACTIVITY IN THE PROSTATE GLAND OF THE GUINEA-PIG<

B. Exintaris ¹, R.J. Lang ², 1 Department of Pharmaceutical Biology & Pharmacology, Victorian College of Pharmacy, Monash University, Parkville, VIC; 2 Department of Physiology, Monash University, Clayton, VIC.

The role of internal Ca²⁺ stores in the generation of the rhythmic electrical activity in the guinea-pig prostate was examined using intracellular microelectrodes and whole-cell voltage-clamp of freshly-isolated single stromal myocytes. Prostate glands were removed from guinea-pigs (250-350g) killed humanely by stunning and exsanguination. Saccular glands were pinned to the bottom of an organ bath (1 ml), which was subsequently mounted on an inverted microscope stage and perfused with physiological saline solution (35°C). The spontaneous electrical events recorded in the stromal smooth muscle consisted of distinct nifedipine-resistant depolarising transients which often triggered 1-3 spikes. Caffeine (1 mM) significantly reduced the frequency of the spontaneous electrical events in the presence or absence of nifedipine. In contrast ryanodine transiently increased slow wave frequency. In freshly dispersed stromal myocytes, caffeine reversibly increased, while ryanodine irreversibly decreased the whole cell Ca²⁺-activated K⁺ current (I_KCa) evoked upon membrane depolarisation to all potentials positive to -40 mV. Cyclopiazonic acid (CPA) transiently depolarised (3-9 mV) the membrane potential of the prostatic stroma in the presence or absence of nifedipine. In nifedipine slow wave frequency transiently increased after several mins exposure to CPA and then slowly decreased thereafter. CPA also slowly significantly reduced I_KCa at all potentials positive to -30 mV. 2-APB, a known blocker of IP₃-mediated Ca release decreased slow wave frequency and reversibly increased I_KCa. U73122 and neomycin also inhibited slow wave discharge as well as the stromal contractions evoked by phenylephrine. Propulsion of the prostatic secretions into the prostatic ducts and urethra is likely to occur via the spontaneous contractions triggered by the myogenic slow wave activity in prostatic smooth muscle. Ryanodine- or IP₃-dependent release of Ca²⁺ from intracellular stores is likely to have a modulatory role in the regulation of the frequency of slow wave activity in the guinea pig prostate.