Expression of the ether-a-go-go (ERG) potassium channel in smooth muscle of the equine gastrointestinal tract and influence on activity of jejunal smooth muscle.

This study investigates the presence and influence of ether-a-go-go (ERG) potassium channels in horse gastrointestinal smooth muscle, particularly focusing on their effect on muscle contraction in the horse’s small intestine (jejunum). The research also studies the impact of ERG channel antagonists, drugs that oppose ERG channel’s effect, including cisapride, a commonly used treatment for postoperative ileus (POI) in horses.

Methods

The researchers performed several tests and procedures for this study:

• Smooth muscle samples were collected from the different segments of the intestinal tract (duodenum, jejunum, ileum, cecum, large colon, and small colon) of 8 horses without gastrointestinal tract disease.
• Immunoblotting was performed on these samples to identify the presence of ERG protein, confirming the expression of ERG channels.
• Jejunal muscle strips were isolated and subjected to isometric stress – a measurement of their contraction – in the presence of ERG channel blockers (E-4031, MK-499, clofilium, and cisapride).
• Plasma samples were obtained from another 3 horses undergoing cisapride treatment for POI following small intestinal surgery. The concentrations of cisapride were measured to check if they are compatible with the initiation of ERG channel blocking.

Results

The study yielded the following findings:

• Immunoblotting detected ERG protein across all examined parts of the horses’ intestinal tract, confirming the expression of ERG channels.
• Among the ERG channel blockers, the selective ERG antagonist E-4031 demonstrated a concentration-dependent increase in the contraction of jejunal muscles. Other ERG blockers including clofilium, MK-499, and cisapride showed a similar effect.
• The effects of E-4031 and cisapride were found not to be additive, indicating they likely target the same mechanism.
• The peak plasma concentrations of cisapride in the treated horses were consistent with ERG channel blocking, suggesting this is the primary mechanism of action for the drug.

Conclusions

The study concluded that ERG potassium channels are indeed present in horse intestinal muscles and significantly influence their motility. Furthermore, these channels appear to be pharmacological targets for drugs like cisapride used in treating POI. These findings may help in the development of newer prokinetic agents – drugs that enhance gastrointestinal motility – and provide insights for treating horses suffering from POI.