Korean J Physiol Pharmacol.  2012 Oct;16(5):297-303. 10.4196/kjpp.2012.16.5.297.

High K(+)-Induced Relaxation by Nitric Oxide in Human Gastric Fundus

• Kim DH
• Kim YC
• Choi W
• Yun HY
• Sung R
• Kim HS
• Kim H
• Yoo RY
• Park SM
• Yun SJ
• Song YJ
• Xu WX
• Lee SJ

• KMID: 1493961
• DOI: http://doi.org/10.4196/kjpp.2012.16.5.297

Abstract

This study was designed to elucidate high K(+)-induced relaxation in the human gastric fundus. Circular smooth muscle from the human gastric fundus greater curvature showed stretch-dependent high K+ (50 mM)-induced contractions. However, longitudinal smooth muscle produced stretch-dependent high K(+)-induced relaxation. We investigated several relaxation mechanisms to understand the reason for the discrepancy. Protein kinase inhibitors such as KT 5823 (1 microM) and KT 5720 (1 microM) which block protein kinases (PKG and PKA) had no effect on high K(+)-induced relaxation. K+ channel blockers except 4-aminopyridine (4-AP), a voltage-dependent K+ channel (KV) blocker, did not affect high K(+)-induced relaxation. However, N(G)-nitro-L-arginine and 1H-(1,2,4)oxadiazolo (4,3-A)quinoxalin-1-one, an inhibitors of soluble guanylate cyclase (sGC) and 4-AP inhibited relaxation and reversed relaxation to contraction. High K(+)-induced relaxation of the human gastric fundus was observed only in the longitudinal muscles from the greater curvature. These data suggest that the longitudinal muscle of the human gastric fundus greater curvature produced high K(+)-induced relaxation that was activated by the nitric oxide/sGC pathway through a KV channel-dependent mechanism.

Keyword

Fundus; High K+; Human stomach; Longitudinal smooth muscle; Nitric oxide; Relaxation

MeSH Terms

4-Aminopyridine
Carbazoles
Contracts
Gastric Fundus
Guanylate Cyclase
Humans
Muscle, Smooth
Muscles
Nitric Oxide
Protein Kinase Inhibitors
Protein Kinases
Pyrroles
Relaxation
4-Aminopyridine
Carbazoles
Guanylate Cyclase
Nitric Oxide
Protein Kinase Inhibitors
Protein Kinases
Pyrroles

Figure

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  Fig. 1 Contractions of circular and longitudinal smooth muscle of the fundus greater curvature (GC). Circular muscle of the fundus GC showed spontaneous contraction (A). In (C) high-K+ produced an initial and a tonic contraction and it reached peak by stepwise stretch (0.8~1 g). ACh (10 µM) produced triphasic contractions in panel (B). Longitudinal muscle of the fundus lesser curvature (LC) obtained from a patient who underwent repetitive gastrectomy showed large high K+-induced relaxation (D). ACh produced contraction in the longitudinal muscle (E).

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  Fig. 2 High K+-induced relaxation of longitudinal smooth muscle in the fundus GC. Longitudinal muscle showed spontaneous (A) and ACh-induced contraction (B) however high K+ produced relaxation (C). High K+-induced relaxation was gradually increased by application of stepwise stretch (C). In (D) SNP (3 and 5 µM) produced relaxation of -3.0 g. High K+ produced relaxation (-1.4 g; Ea) and it was -61% of total relaxation to basal tone (Eb).

• 

  Fig. 3 Effect of inhibitors of K+ channels and protein kinases (PK) on high K+-induced relaxation of longitudinal smooth muscle in the fundus GC. High K+-induced relaxation was not inhibited by tetraethylammonium (TEA, 10 mM) which is known inhibitor of Ca2+-activated K+ channel (KCa channel) (A) and also not by K+ channel blockers cocktail (KBC except 4-AP, see methods; (B), (Ca, Cb). Furthermore, it was not affected by KT5823 and KT5720, blockers of PKG and PKA, respectively (D, E).

• 

  Fig. 4 Involvement of nitric oxide (NO) and soluble guanylyl cyclase (sGC) on high K+-induced relaxation of longitudinal smooth muscle in the fundus GC. In (A, B) high K+ produced relaxation in longitudinal muscle in the fundus GC. However, L-NNA (100 µM) and ODQ (10 µM) blocked and reversed high K+-induced relaxation to contraction (A, B). The data were summarized in (C, D).

• 

  Fig. 5 Effects of 4-aminopyridine (4-AP) on high K+-induced relaxation of longitudinal smooth muscle in the fundus GC. Most high K+-induced relaxation were blocked or reversed to contraction (A), though some were not, by pretreatment of 4-AP with nerve blockers cocktail (NBC, see methods; C). In (B) effect of 4-AP (5 mM) on high K+-induced relaxation was summarized. In the presence of 4-AP (5 mM), high K+-induced relaxation was inhibited. In the presence of NBC and 4-AP, the percent relaxation of high K+-induced relaxation was suppressed (Ca) to -32% of the control (Cb).

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  Fig. 6 High K+-induced response in the fundus LC. Contractile properties of circular and longitudinal smooth muscles of the fundus LC were investigated too. Circular muscle of the fundus LC showed high K+-induced contraction (A). Meanwhile, high K+ produced an initial contraction followed by an weak contraction in longitudinal muscle of the fundus LC (B).

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