Characterization of the off response to electrical field stimulation in gallbladder smooth muscle

Background. Low-frequency electrical stimulation of intramural nerves of gu t smooth muscle produces an "off response," that is, a contraction that occ urs after electrical field stimulation (EFS) of the intramural nerves is st opped. The off response coincides with a depolarization of the muscle follo wing an EFS-induced hyperpolarization of that muscle. The aims of our study were to determine if the off response is present in gallbladder smooth mus cle and to determine the mechanisms involved in this nerve-mediated respons e. Materials and methods. Gallbladder strips from opossums were placed in Kreb s solution and passed through bipolar ring electrodes for EFS of intramural nerves, and isometric force measurements were recorded. Dose-response curv es were determined with N-G-nitro-L-arginine (L-NNA) a competitive inhibito r of nitric oxide (NO) synthase; 1H-[1,2,4] oxadiazolol[4,3a]quinoxalin-1-o ne (ODQ), an inhibitor of soluble guanylate cyclase; and oxyhemoglobin, a s cavenger of nitric oxide. Results. A contraction termed the off response occurred shortly after EFS e nded. The off response was abolished with tetrodotoxin and atropine. The am plitude of the off response increased with increasing voltage. The amplitud e of the off response decreased by 41% with L-NNA 1.5 mM. Preincubation of the tissue with L-arginine (1 mM) prevented the inhibition of amplitude see n with L-NNA. The amplitude of the off response decreased by 43% with oxyhe moglobin (40 mu M) and by 56% with ODQ (250 mu M). Conclusion. We conclude that the off response is present in gallbladder smo oth muscle after low-frequency EFS. NO may be a mediator of this off respon se and of nonadrenergic noncholinergic responses in gallbladder smooth musc le, (C) 2000 Academic Press.