Regulation of spontaneous activity in rabbit corpus cavernosum myocytes by nitric oxide
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چکیده
The aim of the present study is two fold. Firstly, to determine if the nitric oxide (NO)/cGMP pathway can modulate spontaneous transient inward and outward currents (STICs and STOCs), in rabbit corpus cavernosum smooth muscle. Secondly, to see if nitric oxide can effect intracellular calcium oscillations observed in these cells. Male New Zealand white rabbits were humanely killed with an injection of pentobarbitone (I.V.), and the corpus cavernosum was dissected from the penis and cut into 1 mm3 pieces. From this, single smooth muscle cells were isolated in a medium containing collagenase as described previously [1]. The cells were then studied at 37°C using the perforated patch technique. When cells were held under voltage clamp at -60 mV, using caesium containing pipettes, over 70% fired STICs. These events were shown to be carried by a Ca2+-activated Clconductance, and were sensitive to inhibition of IP3-mediated Ca2+-release [1]. Modulation by the NO/cGMP pathway was investigated by applying nitrosocysteine, 3-(5-hydroxymethyl-2furyl)-1-benzyl indazole (YC-1), and 8-bromo cGMP, all three of which abolished STIC activity. In addition, the protein kinase G 1 (GK1) specific activator SP-8-Br-PETcGMPS (25 and 100 μM), significantly reduced STICs. This provides one possible mechanism whereby the NO/ cGMP pathway could inhibit tone in corpus cavernosum smooth muscle.
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