Involvement Of Trpv1 And Trpa1 In The Modulation Of Pacemaker Potentials In The Mouse Ileum

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 mu M to 3 mM), resiniferatoxin (300 mu M), capsazepine (100-300 mu M), allyl isothiocyanate (300 mu M), isovelleral (300 mu M), icilin (300 mu M), A-967,079 (10 mu M), AP18 (20 mu M) and HC-030,031 (50 mu M) significantly reduced the pacemaker frequency and increased the waveform period relative to the baseline. Conversely, ruthenium red (300 mu M) significantly increased the pacemaker frequency and reduced the waveform period. Capsaicin (3 mM) and AP18 (20 mu M) also significantly reduced the propagation velocity. However, all tested antagonists failed to inhibit the effects of agonists. AMG9810 (300 mu M), but not A-967,079 (300 mu M), 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.