Abstract
NO released by myenteric neurons controls the off contraction induced by electrical field stimulation (EFS) in distal esophageal smooth muscle, but in the presence of nitric oxide synthase (NOS) inhibitor, L-NAME, contraction by EFS occurs at the same time. The authors investigated the intracellular signaling pathways related with G protein and ionic channel EFS-induced contraction using cat esophageal muscles. EFS-induced contractions were significantly suppressed by tetrodotoxin (1 microM) and atropine (1 microM). Furthermore, nimodipine inhibited both on and off contractions by EFS in a concentration dependent meaner. The characteristics of 'on' and 'off' contraction and the effects of G-proteins, phospholipase, and K(+) channel on EFS-induced contraction in smooth muscle were also investigated. Pertussis toxin (PTX, a G(i) inactivator) attenuated both EFS-induced contractions. Cholera toxin (CTX, G(s) inactivator) also decreased the amplitudes of EFS-induced off and on contractions. However, phospholipase inhibitors did not affect these contractions. Pinacidil (a K(+) channel opener) decreased these contractions, and tetraethylammonium (TEA, K(+) (Ca) channel blocker) increased them. These results suggest that EFS-induced on and off contractions can be mediated by the activations Gi or Gs proteins, and that L-type Ca(2+) channel may be activated by G-protein alpha subunits. Furthermore, K(+) (Ca)-channel involve in the depolarization of esophageal smooth muscle. Further studies are required to characterize the physiological regulation of Ca(2+) channel and to investigate the effects of other K(+) channels on EFS-induced on and off contractions.