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Characterization of the off response to electrical field stimulation in gallbladder smooth muscle
J J Cullen1, M M Hinkhouse, J L Conklin
1Department of Surgery, University of Iowa, Iowa City, Iowa 52242, USA.
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.
Insights
The gallbladder smooth muscle exhibits an "off response" contraction after nerve stimulation. Nitric oxide (NO) appears to mediate this response, suggesting a role in nonadrenergic, noncholinergic signaling.
Area of Science:
- Gastroenterology
- Neurogastroenterology
- Smooth Muscle Physiology
Background:
- Low-frequency electrical field stimulation (EFS) of gut nerves causes an
- off response
- contraction after stimulation ceases.
- This response is linked to muscle depolarization following hyperpolarization.
Purpose of the Study:
- To investigate the presence of the
- off response
- in gallbladder smooth muscle.
- To elucidate the underlying neural mechanisms of this response.
Main Methods:
- Opossum gallbladder strips underwent EFS via bipolar ring electrodes.
- Isometric force measurements were recorded.
- Involvement of nitric oxide (NO) pathways was assessed using L-NNA, ODQ, and oxyhemoglobin.
Main Results:
- An
- off response
- contraction was observed after EFS cessation.
- The response was blocked by tetrodotoxin and atropine.
- Inhibition of NO synthase (L-NNA), guanylate cyclase (ODQ), and NO scavenging (oxyhemoglobin) significantly reduced the off response amplitude.
Conclusions:
- The
- off response
- is present in gallbladder smooth muscle following low-frequency EFS.
- Nitric oxide (NO) is implicated as a mediator of this response.
- NO may play a role in nonadrenergic, noncholinergic signaling in the gallbladder.