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. 2003 Sep;9(9):2054-9.
doi: 10.3748/wjg.v9.i9.2054.

Role of calcium-activated potassium currents in CNP-induced relaxation of gastric antral circular smooth muscle in guinea pigs

Hui-Shu Guo  1 , Zheng-Xu Cai, Hai-Feng Zheng, Xiang-Lan Li, Yi-Feng Cui, Zuo-Yu Wang, Wen-Xie Xu, Sang-Jin Lee, Young-Chul Kim
Affiliations

Role of calcium-activated potassium currents in CNP-induced relaxation of gastric antral circular smooth muscle in guinea pigs

Hui-Shu Guo et al. World J Gastroenterol. 2003 Sep.

Abstract

Aim: To investigate ion channel mechanism in CNP-induced relaxation of gastric circular smooth muscle in guinea pigs.

Methods: Spontaneous contraction of gastric smooth muscle was recorded by a four -channel physiograph. The whole cell patch-clamp technique was used to record calcium-activated potassium currents and membrane potential in the gastric myocytes isolated by collagenase.

Results: C-type natriuretic peptide (CNP) markedly inhibited the spontaneous contraction in a dose-dependent manner in gastric circular smooth muscle in guinea pigs. Ly83583, an inhibitor of guanylate cyclase, weakened CNP-induced inhibition on spontaneous contraction but Zaparinast, an inhibitor of cGMP sensitive phosphoesterase, potentiated CNP-induced inhibition in gastric circular smooth muscles. The inhibitory effects of CNP on spontaneous contraction were blocked by tetrathylammonium (TEA), a nonselective potassium channel blocker. CNP hyperpolarized membrane potential from -60.0 mV+/-2.0 mV to -68.3 mV+/-3.0 mV in a single gastric myocyte. CNP increased calcium-activated potassium currents (I(K(ca))) in a dose-dependent manner in gastric circular myocytes. CNP also increased the spontaneously transient outward currents (STOCs). Ly83583 partly blocked CNP-induced increase of calcium-activated potassium currents, but Zaparinast potented the effect.

Conclusion: CNP inhibits spontaneous contraction, and potassium channel may be involved in the process in gastric circular smooth muscle of guinea pigs. CNP-induced increase of I(K(ca)) is mediated by a cGMP dependent pathway.

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Figures

Figure 1
Figure 1
Effect of CNP on spontaneous contraction of gastric circular smooth muscle in a dose-dependent manner in guinea pigs. aP < 0.01 vs 10-8 mol·L-1 group.
Figure 2
Figure 2
Effect of Ly83583 on CNP-induced inhibition in gastric circular smooth muscle of guinea pigs. aP < 0.05 vs CNP group.
Figure 3
Figure 3
Effect of Zaparinast on CNP-induced inhibition in gastric circular smooth muscle of guinea pigs. aP < 0.05 vs CNP group.
Figure 4
Figure 4
Effect of TEA on CNP-induced inhibition in gastric circular smooth muscle of guinea pigs. aP < 0.01 vs CNP group.
Figure 5
Figure 5
Effect of CNP on membrane potential of gastric circular myocytes in guinea pigs. aP < 0.05 vs Control group.
Figure 6
Figure 6
Effect of CNP on Ik(ca) in gastric circular smooth muscle of guinea pigs. aP < 0.05 vs Control group; bP < 0.01 vs Control group.
Figure 7
Figure 7
Dose-dependent manner of CNP calcium-activated potassium currents in gastric circular smooth muscle of guinea pigs. aP < 0.05 vs Control group, bP < 0.01 vs Control group.
Figure 8
Figure 8
Effect of CNPon STOCs in gastric circular smooth muscle of guinea pigs.
Figure 9
Figure 9
Effect of Ly83583 on CNP-induced increase of calcium-activated potassium currents in gastric circular smooth muscle of guinea pigs. aP < 0.05 vs Ly group, bP < 0.01 vs Ly + CNP group.
Figure 10
Figure 10
Effect of Zaparinast on CNP-induced increase of calcium-activated potassium currents in gastric circular smooth muscle of guinea pigs. aP < 0.01 vs Zap group, bP < 0.01 vs Zap + CNP group.
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