Involvement of TRPV1 and TRPA1 in the modulation of pacemaker potentials in the mouse ileum

Julia Y H Liu; Peng Du; Zengbing Lu; Jeng S C Kung; Ianto B Huang; Jessica C M Hui; Heidi S H Ng; M P Ngan; Dexuan Cui; Bin Jiang; S W Chan; John A Rudd

doi:10.1016/j.ceca.2021.102417

Involvement of TRPV1 and TRPA1 in the modulation of pacemaker potentials in the mouse ileum

Cell Calcium. 2021 Apr 30:97:102417. doi: 10.1016/j.ceca.2021.102417. Online ahead of print.

Authors

Julia Y H Liu¹, Peng Du², Zengbing Lu³, Jeng S C Kung³, Ianto B Huang³, Jessica C M Hui³, Heidi S H Ng³, M P Ngan³, Dexuan Cui³, Bin Jiang⁴, S W Chan⁴, John A Rudd³

Affiliations

¹ School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China. Electronic address: liuyh@cuhk.edu.hk.
² Auckland Bioengineering Institute, University of Auckland, New Zealand.
³ School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China.
⁴ School of Health Sciences, Caritas Institute of Higher Education, Tseung Kwan O, Hong Kong SAR, China.

PMID: 33962108
DOI: 10.1016/j.ceca.2021.102417

Abstract

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.

Keywords: Microelectrode array; Pacemaker potentials; Slow wave; TRPA1; TRPV1.