Physiological function and molecular composition of ATP-sensitive K + channels in human gastric smooth muscle

J Smooth Muscle Res. 2020;56(0):29-45. doi: 10.1540/jsmr.56.29.

Abstract

Gastric motility is controlled by slow waves. In general, the activation of the ATP-sensitive K+ (KATP) channels in the smooth muscle opposes the membrane excitability and produces relaxation. Since metabolic inhibition and/or diabetes mellitus are accompanied by dysfunctions of gastric smooth muscle, we examined the possible roles of KATP channels in human gastric motility. We used human gastric corpus and antrum smooth muscle preparations and recorded the mechanical activities with a conventional contractile measuring system. We also identified the subunits of the KATP channels using Western blot. Pinacidil (10 μM), a KATP channel opener, suppressed contractions to 30% (basal tone to -0.2 g) of the control. The inhibitory effect of pinacidil on contraction was reversed to 59% of the control by glibenclamide (20 μM), a KATP channel blocker. The relaxation by pinacidil was not affected by a pretreatment with L-arginine methyl ester, tetraethylammonium, or 4-aminopyridine. Pinacidil also inhibited the acetylcholine (ACh)-induced tonic and phasic contractions in a glibenclamide-sensitive manner (42% and 6% of the control, respectively). Other KATP channel openers such as diazoxide, cromakalim and nicorandil also inhibited the spontaneous and ACh-induced contractions. Calcitonin gene-related peptide (CGRP), a gastric neuropeptide, induced muscle relaxation by the activation of KATP channels in human gastric smooth muscle. Finally, we have found with Western blot studies, that human gastric smooth muscle expressed KATP channels which were composed of Kir 6.2 and SUR2B subunits.

Keywords: ATP-sensitive K+ (KATP) channel; CGRP; gastric antrum and corpus; human stomach.

MeSH terms

  • Calcitonin Gene-Related Peptide / pharmacology
  • Gastrointestinal Motility / drug effects
  • Glyburide / pharmacology
  • Humans
  • In Vitro Techniques
  • KATP Channels / antagonists & inhibitors
  • KATP Channels / metabolism*
  • KATP Channels / physiology*
  • Muscle Contraction / drug effects
  • Muscle Relaxation / drug effects
  • Muscle, Smooth / chemistry
  • Muscle, Smooth / physiology*
  • Stomach / physiology*

Substances

  • KATP Channels
  • Calcitonin Gene-Related Peptide
  • Glyburide