Key result
Patch clamp recordings of guinea pig prostate stromal myocytes identified a rapidly activating nifedipine-sensitive Ca current and complex K selective outward currents modulated by intracellular Ca.
Characterization of ion channels in guinea pig prostate stromal myocytes identifies specific calcium and potassium currents that could be targeted to modulate muscle tone.
May identify targets to modulate prostate stromal tone; leaves open translation to human lower urinary tract symptoms.
PURPOSE: We characterized membrane ionic currents underlying the action potential in single myocytes freshly isolated from the stroma of the guinea pig prostate. MATERIAL AND METHODS: Whole cell and single channel currents were recorded in single stromal smooth muscle cells using standard patch clamp techniques. RESULTS: : A rapidly activating, nifedipine (1 microM) sensitive Ca current was recorded in CsCl (130 mM) filled myocytes at potentials positive to -50 mV This current was half maximally activated at -22 mV and half maximally inactivated at -53 mV. In KCl (130 mM) filled myocytes membrane depolarization evoked a complex set of K selective outward currents, consisting of a rapidly activating transient outward current (IKto) followed by a more slowly developing transient outward current (IP2), which decayed to a steady state current (ISS). Tetraethylammonium (1 mM), a blocker of large conductance, Ca activated K channels, substantially blocked IP2 and ISS. Initial IKto was half maximally activated at -5 mV, half maximally inactivated at -65 mV and blocked by 4-aminopyridine (IC50 0.8 mM). IP2 and ISS were decreased by ryanodine (10 microM) or cyclopiazonic acid (10 microM) and increased by caffeine (1 mM), suggesting that Ca release from internal stores participates in the activation of these large conductance, Ca activated K channel currents. CONCLUSIONS: We speculate that membrane currents characterized in stromal myocytes underlie the generation of simple action potentials triggered during the slow wave recorded in the intact guinea pig prostate and pharmacological manipulation of IKto and IP2 may well provide a selective avenue of modulating stromal excitability and muscle tone.
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Lang et al. (2004) studied this question. Pharmacological manipulation (nifedipine, TEA, 4-AP, ryanodine, cyclopiazonic acid, caffeine) was evaluated on Characterization of membrane ionic currents. Patch clamp recordings of guinea pig prostate stromal myocytes identified a rapidly activating nifedipine-sensitive Ca current and complex K selective outward currents modulated by intracellular Ca.
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