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  • Author or Editor: Kenton M. Sanders x
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Abstract

Objective—To evaluate electrical activity of jejunal circular muscle in horses and characterize electrical responses to stimulation by intrinsic inhibitory neurons.

Sample Population—Portions of jejunum obtained from horses euthanatized for reasons other than gastrointestinal tract disease.

Procedure—Isolated circular muscle preparations were perfused with oxygenated modified Krebs solution. Glass microelectrodes were used for intracellular recording of membrane potentials from single smooth muscle cells. Electrical activity and responses to electrical field stimulation (EFS) of intrinsic neurons in the presence of guanethidine and atropine were recorded. Mediators of responses to nerve stimulation were also evaluated, using N-nitro-L-arginine methyl ester (L-NAME) and apamin.

Results—Mean resting membrane potential (RMP) was 41.5 ± 1.8 mV. Small membrane potential oscillations were observed in muscle cells. Single or multiple action potentials were often superimposed on the peaks of these oscillations. Spontaneous oscillations and action potentials were blocked by nifedipine. Transient hyperpolarizations of smooth muscle cell membrane potentials (inhibitory junction potentials [IJP]) were observed in response to electrical field stimulation. The IJP evoked by stimulus trains consisted of an initial fast component followed by a slow component. The L-NAME did not have a significant effect on RMP and did not significantly affect the fast component of IJP at any stimulus frequency tested. In contrast, L-NAME abolished the slow component of IJP observed after trains of pulses. In the continued presence of L-NAME, apamin had no significant effect on RMP but effectively reduced the fast component of IJP.

Conclusions and Clinical Relevance—Findings suggest that inhibitory neurotransmitters supplying equine jejunum act through different ionic mechanisms. Understanding these mechanisms may suggest new therapeutic targets for treatment of motility disorders. (Am J Vet Res 2000;61:362–368)

Full access
in American Journal of Veterinary Research

Abstract

Objectives

To evaluate the role of nitric oxide (NO), vasoactive intestinal peptide (VIP), and a transmitter acting through an apamin-sensitive mechanism in mediating inhibitory transmission in the equine jejunal circular muscle, and to determine the distribution of VIP-and NO-producing nerve fibers in the myenteric plexus and circular muscle.

Procedure

Circular muscle strips were suspended in tissue baths containing an oxygenated modified Krebs solution and attached to isometric force transducers. Responses to electrical field stimulation (EFS), tetrodotoxin, the NO antagonists l-N-nitro-arginine-methyl-ester (L-NAME) and N-nitro-l-arginine, apamin, VIP, authentic NO, and the NO donar sodium nitroprusside were tested. Immunostaining for VIP-like and NADPH diaphorase histochemical staining were performed on paraformaldehyde-fixed tissue.

Results

Subpopulations of myenteric neurons and nerve fibers in the circular muscle were positive for NADPH diaphorase and VIP-like staining. EFS caused a frequency-dependent inhibition of contractile activity. Tetrodotoxin prevented the EFS-induced inhibition of contractions. L-NAME (200 μM) and apamin 0.3 μM) significantly (P < 0.01) reduced EFS-stimulated inhibition of contractile activity at most frequencies tested. The effects of L-NAME and apamin were additive. In their combined presence, EFS induced excitation instead of inhibition (196.7% increase at 5 Hz, n = 28, P < 0.01). Inhibition of contractile activity by EFS was mimicked by sodium nitroprusside. Authentic NO (3-6 μM) abolished contractile activity. VIP induced a dose-dependent inhibition of contractile activity (89.1 ± 6.3% reduction at approximately 0.3 μM, n = 16). Antagonism of NO synthesis did not alter the response to VIP.

Conclusion

NO, VIP, and a substance acting through an apamin-sensitive mechanism appear to comediate inhibitory transmission in the equine jejunal circular muscle.

Clinical Relevance

These findings may suggest new therapeutic targets for motility disorders, such as agents that inhibit the synthesis or actions of NO. (Am J Vet Res 1996;57:1206-1213)

Free access
in American Journal of Veterinary Research