It was investigated whether Ca^2+ and K^+ channels were involved in the inhibitory action of nitric oxide (NO) on the contractile and slow wave activity of guinea pig gastric antral circular muscle.
The gastric antral circular muscle showed spontaneous phasic contraction and slow wave. NO donors, 3-morpholinosydnonimine hydrochloride (SIN-1, 0.01∼100 μM) and S-nitroso-L-cysteine (CysNO, 0.001∼10 μM), reduced not only the amplitude of phasic contraction but also that of slow wave in a concentration-dependent manner. Both the perfusion of Ca^2+-free solution and the administration of Ni^2+, a nonselective Ca^2+ channel blocker, reduced the phasic contraction as well as the amplitude and frequency of the slow wave. The effects of these treatments were similar to those of NO donors. Nifedipine (10 μM), a specific L-type Ca^2+ channel blocker, abolished the phasic contraction and remarkably reduced the plateau of slow wave but had no profound effect on the upstroke of slow wave. In the whole-cell patch clamp mode, CysNO shifted the steady-state activation curve for L-type Ca^2+ current to the right and the steady-state inactivation curve to the left. Pretreatment of various K^+ channel blockers such as tetraethylammonium (1 mM), 4-aminopyridine (0.5 mM), glibenclamide (10 mM), apamin (0.1 μM), and iberiotoxin (0.1 μM) did not affect the inhibitory action of SIN-1.
These results suggest that NO donors suppress mechanical and electrical activity of guinea pig gastric antral circular muscle by inhibition of L-type Ca^2+ channel rather than by activation of K^+ channels.
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