The Effect of NO Donor on Contraction, Cytosolic Ca<SUP>2&#8290;</SUP> Level and Ionic Currents in Guinea-pig Ileal Smooth Muscle

The Effect of NO Donor on Contraction, Cytosolic Ca<SUP>2&#8290;</SUP> Level and Ionic Currents in Guinea-pig Ileal Smooth Muscle

<P> This study was designed to clarify the mechanism of the inhibitory action of a nitric oxide (NO) donor, 3-morpholino-sydnonimine (SIN-1), on contraction, cytosolic Ca<SUP>2&#8290;</SUP> level ([Ca<SUP>2&#8290;</SUP>]<SUB>i</SUB>), and ionic currents in guinea-pig ileum. SIN-1 (0.01∼100μM) inhibited 25 mM KCl- or histamine (10μM)-induced contraction in a concentration-dependent manner. SIN-1 reduced both the 25 mM KCl- and the histamine-stimulated increases in muscle tension in parallel with decreased [Ca<SUP>2&#8290;</SUP>]<SUB>i</SUB>. Using the patch clamp technique with a holding potential of &#8291;60 mV, SIN-1 (10μM) decreased peak Ba currents (I<SUB>Ba</SUB>) by 30.9&#8273;5.4% (n=6) when voltage was stepped from &#8291;60 mV to &#8290;10 mV and this effect was blocked by ODQ (1μM), a soluble guanylyl cyclase inhibitor. Cu/Zn SOD (100 U/ml), the free radical scavenger, had little effect on basal I<SUB>Ba</SUB>, and SIN-1 (10μM) inhibited peak I<SUB>Ba</SUB> by 32.4&#8273;5.8% (n=5) in the presence of Cu/Zn SOD. In a cell clamped at a holding-potential of &#8291;40 mV, application of 10μM histamine induced an inward current. The histamine-induced inward current was markedly and reversibly inhibited by 10μM SIN-1, and this effect was abolished by ODQ (1μM). In addition, SIN-1 markedly increased the depolarization-activated outward K<SUP>&#8290;</SUP> currents in the all potential ranges. We concluded that SIN-1 inhibits smooth muscle contraction mainly by decreasing [Ca<SUP>2&#8290;</SUP>]<SUB>i</SUB> resulted from the inhibition of L-type Ca<SUP>2&#8290;</SUP> channels and the inhibition of nonselective cation currents and/or by the activation of K<SUP>&#8290;</SUP> currents via a cGMP-dependent pathway.