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Involvement of TRPV1 and TRPA1 in the modulation of pacemaker potentials in the mouse ileum
Julia Y H Liu1, Peng Du2, Zengbing Lu1
1School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China.
Background:
The roles of transient receptor potential cation channel, subfamily V, member 1 (TRPV1) and subfamily A, member 1 (TRPA1) in mechanisms of gastrointestinal motility are complex. This study aimed to clarify the effects of several TRPV1 and TRPA1 ligands on the electrical potentials generated by pacemaker cells in the mouse-isolated ileum.
Method:
The pacemaker potentials of ileal segments of mice were recorded extracellularly using a 60-channel microelectrode array. The dominant frequencies, average waveform periods and propagation velocities were quantified. The effects of TRPV1 and TRPA1 agonist and antagonist were compared with the baseline recordings.
Results:
The electrophysiological recordings showed that capsaicin (30 μM to 3 mM), resiniferatoxin (300 μM), capsazepine (100-300 μM), allyl isothiocyanate (300 μM), isovelleral (300 μM), icilin (300 μM), A-967,079 (10 μM), AP18 (20 μM) and HC-030,031 (50 μM) significantly reduced the pacemaker frequency and increased the waveform period relative to the baseline. Conversely, ruthenium red (300 μM) significantly increased the pacemaker frequency and reduced the waveform period. Capsaicin (3 mM) and AP18 (20 μM) also significantly reduced the propagation velocity. However, all tested antagonists failed to inhibit the effects of agonists. AMG9810 (300 μM), but not A-967,079 (300 μM), significantly inhibited the increases in pacemaker frequency caused by increased temperatures.
Conclusion:
Our findings suggest that TRPV1 and TRPA1 play a minor role in regulating pacemaker potentials and that at non-specific actions at other TRP and ion channels most likely contributed to the overall effects on the electrophysiological recordings that we observed.
Insights
Transient Receptor Potential Vanilloid 1 (TRPV1) and Transient Receptor Potential Ankyrin 1 (TRPA1) channels appear to have minor roles in mouse ileum pacemaker activity. Non-specific actions on other channels likely explain observed electrophysiological effects.
Area of Science:
- Gastroenterology
- Neuroscience
- Physiology
Background:
- The roles of Transient Receptor Potential Cation Channel, Subfamily V, Member 1 (TRPV1) and Subfamily A, Member 1 (TRPA1) in gastrointestinal motility are not fully understood.
- This study investigated the impact of various TRPV1 and TRPA1 ligands on the electrical activity of pacemaker cells in the mouse ileum.
Purpose of the Study:
- To clarify the effects of TRPV1 and TRPA1 ligands on electrical potentials in mouse ileum pacemaker cells.
- To determine the specific roles of TRPV1 and TRPA1 in regulating gastrointestinal electrical activity.
Main Methods:
- Extracellular recordings of ileal pacemaker potentials using a 60-channel microelectrode array in mouse ileum segments.
- Quantification of dominant frequencies, waveform periods, and propagation velocities.
- Comparison of effects of TRPV1 and TRPA1 agonists and antagonists against baseline recordings.
Main Results:
- TRPV1 and TRPA1 agonists (capsaicin, resiniferatoxin, allyl isothiocyanate, isovelleral, icilin) and antagonists (capsazepine, A-967,079, AP18, HC-030,031) generally reduced pacemaker frequency and increased waveform period.
- Ruthenium red, a TRPV1 antagonist, increased pacemaker frequency and reduced waveform period.
- Tested antagonists did not inhibit agonist effects, and AMG9810 inhibited temperature-induced frequency increases, suggesting non-specific channel actions.
Conclusions:
- TRPV1 and TRPA1 appear to play a minor role in regulating mouse ileum pacemaker potentials.
- Observed electrophysiological effects are likely due to non-specific actions on other Transient Receptor Potential (TRP) and ion channels rather than specific TRPV1 or TRPA1 activity.
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