The effect of NO donor on contraction, cytosolic Ca2+ level and ionic currents in guinea-pig ileal smooth muscle.
- Author:
Seong Chun KWON
1
;
Ki Young PARK
;
Duck Sun AHN
;
Young Ho LEE
;
Bok Soon KANG
Author Information
1. Department of Physiology, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul, South Korea.
- Publication Type:Original Article
- MeSH:
Cytosol*;
Guanylate Cyclase;
Histamine;
Humans;
Ileum;
Muscle Tonus;
Muscle, Smooth*;
Nitric Oxide;
Tissue Donors*
- From:The Korean Journal of Physiology and Pharmacology
2000;4(1):33-40
- CountryRepublic of Korea
- Language:English
-
Abstract:
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 Ca2+ level ((Ca2+)i), and ionic currents in guinea-pig ileum. SIN-1 (0.01~100 micrometer) inhibited 25 mM KCl- or histamine (10 micrometer)-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 (Ca2+)i. Using the patch clamp technique with a holding potential of -60 mV, SIN-1 (10 micrometer) decreased peak Ba currents (IBa) by 30.9+/-5.4% (n=6) when voltage was stepped from -60 mV to +10 mV and this effect was blocked by ODQ (1 micrometer), a soluble guanylyl cyclase inhibitor. Cu/Zn SOD (100 U/ml), the free radical scavenger, had little effect on basal IBa, and SIN-1 (10 micrometer) inhibited peak IBa by 32.4+/-5.8% (n=5) in the presence of Cu/Zn SOD. In a cell clamped at a holding-potential of -40 mV, application of 10 micrometer histamine induced an inward current. The histamine-induced inward current was markedly and reversibly inhibited by 10 micrometer SIN-1, and this effect was abolished by ODQ (1 micrometer). In addition, SIN-1 markedly increased the depolarization-activated outward K+ currents in the all potential ranges. We concluded that SIN-1 inhibits smooth muscle contraction mainly by decreasing (Ca2+)i resulted from the inhibition of L-type Ca2+ channels and the inhibition of nonselective cation currents and/or by the activation of K+ currents via a cGMP-dependent pathway.
