Effects of endothelin-1 on the membrane potential and slow waves in circular smooth muscle of rat gastric antrum

J Smooth Muscle Res. 2004 Oct;40(4-5):199-210. doi: 10.1540/jsmr.40.199.

Abstract

Electrophysiological effects of endothelin-1 (ET-1) on circular smooth muscle of rat gastric antrum were investigated by using intracellular membrane potential recording techniques. ET-1 (10 nM) caused an initial hyperpolarization of the membrane which was followed by a sustained depolarization. ET-1 also increased the frequency but not the amplitude of slow waves. In the presence of the endothelin type A (ETA) receptor antagonist, BQ123 (1 microM), ET-1 (10 nM) depolarized the membrane and increased the frequency of slow waves, but without the initial hyperpolarization. The selective endothelin type B (ETB) receptor agonist, sarafotoxin S6c (10 nM), also depolarized the membrane and increased the frequency of slow waves. In the presence of the ETB receptor antagonist, BQ788 (1 microM), ET-1 (10 nM) hyperpolarized the membrane. However, in the presence of BQ788, ET-1 caused neither the depolarization nor the increase in the frequency of the slow waves. The ET-1-induced hyperpolarization was completely abolished by apamin (0.1 microM). In the presence of apamin, ET-1 depolarized the membrane and increased the frequency of slow waves. The ET-1-induced depolarization was significantly attenuated by 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS, 0.3 mM). The increase of the frequency by ET-1 was observed both in the presence and absence of DIDS. These results suggest that, ET-1 hyperpolarizes the membrane by the activation of Ca2+-activated K+ channels via ETA receptors, and depolarizes the membrane by the activation of Ca2+-activated Cl- channels via ETB receptors. ET-1 also appears to increase the frequency of slow waves via ETB receptors, however this mechanism would seem to be independent of membrane depolarization.

MeSH terms

  • 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / pharmacology
  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Animals
  • Apamin / pharmacology
  • Electromyography
  • Endothelin-1 / pharmacology*
  • Male
  • Muscle, Smooth / drug effects*
  • Muscle, Smooth / physiology*
  • Potassium Channels, Calcium-Activated / physiology
  • Pyloric Antrum / drug effects*
  • Pyloric Antrum / physiology*
  • Rats
  • Receptor, Endothelin A / physiology
  • Receptor, Endothelin B / physiology

Substances

  • Endothelin-1
  • Potassium Channels, Calcium-Activated
  • Receptor, Endothelin A
  • Receptor, Endothelin B
  • Apamin
  • 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid