Effects of endothelin-1 on the membrane potential and slow waves in circular smooth muscle of rat gastric antrum.
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.
Imaeda
Kenro
K
Department of Internal Medicine and Bioregulation, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan. kimaeda@med.nagoya-cu.ac.jp
Kato
Takashi
T
Okayama
Naotsuka
N
Imai
Seiji
S
Sasaki
Makoto
M
Kataoka
Hiromi
H
Nakazawa
Takahiro
T
Ohara
Hirotaka
H
Kito
Yoshihiko
Y
Itoh
Makoto
M
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D004576:Electromyography; D019332:Endothelin-1 / Q000494:pharmacology*; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology*; D024681:Potassium Channels, Calcium-Activated / Q000502:physiology; D011706:Pyloric Antrum / Q000187:drug effects* / Q000502:physiology*; D051381:Rats; D044022:Receptor, Endothelin A / Q000502:physiology; D044023:Receptor, Endothelin B / Q000502:physiology
D019332:Endothelin-1; D024681:Potassium Channels, Calcium-Activated; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D001030:Apamin; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid