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

BACKGROUND

Low-frequency electrical stimulation of intramural nerves of gut smooth muscle produces an "off response," that is, a contraction that occurs after electrical field stimulation (EFS) of the intramural nerves is stopped. The off response coincides with a depolarization of the muscle following an EFS-induced hyperpolarization of that muscle. The aims of our study were to determine if the off response is present in gallbladder smooth muscle and to determine the mechanisms involved in this nerve-mediated response.

MATERIALS AND METHODS

Gallbladder strips from opossums were placed in Krebs solution and passed through bipolar ring electrodes for EFS of intramural nerves, and isometric force measurements were recorded. Dose-response curves were determined with N(G)-nitro-L-arginine (L-NNA) a competitive inhibitor of nitric oxide (NO) synthase; 1H-¿1,2,4ŏxadiazolol¿4, 3aquinoxalin-1-one (ODQ), an inhibitor of soluble guanylate cyclase; and oxyhemoglobin, a scavenger of nitric oxide.

RESULTS

A contraction termed the off response occurred shortly after EFS ended. The off response was abolished with tetrodotoxin and atropine. The amplitude of the off response increased with increasing voltage. The amplitude 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 seen with L-NNA. The amplitude of the off response decreased by 43% with oxyhemoglobin (40 microM) and by 56% with ODQ (250 microM).

CONCLUSION

We conclude that the off response is present in gallbladder smooth muscle after low-frequency EFS. NO may be a mediator of this off response and of nonadrenergic noncholinergic responses in gallbladder smooth muscle.