Mechanical activation of vagal afferents involves opposing cation and TREK1 currents and NO regulation.

Autor: Park SJ; Gastrointestinal Disease Research Unit, Kingston General Hospital, Queen's University, Kingston, ON, K7L2V7, Canada., Zides CG; Gastrointestinal Disease Research Unit, Kingston General Hospital, Queen's University, Kingston, ON, K7L2V7, Canada., Beyak MJ; Gastrointestinal Disease Research Unit, Kingston General Hospital, Queen's University, Kingston, ON, K7L2V7, Canada.
Jazyk: angličtina
Zdroj: Canadian journal of physiology and pharmacology [Can J Physiol Pharmacol] 2023 Oct 01; Vol. 101 (10), pp. 521-528. Date of Electronic Publication: 2023 Jun 13.
DOI: 10.1139/cjpp-2022-0345
Abstrakt: Vagal afferents convey signals of mechanical stimulation in the gut to the brain, which is essential for the regulation of food intake. However, ion channels sensing mechanical stimuli are not fully understood. This study aimed to examine the ionic currents activated by mechanical stimulation and a possible neuro-modulatory role of nitric oxide on vagal afferents. Nodose neuronal currents and potentials, and intestinal afferent firing by mechanical stimulation were measured by whole-cell patch clamp, and in vitro afferent recording, respectively. Osmotically activated cation and two-pore domain K + currents were identified in nodose neurons. The membrane potential displayed a biphasic change under hypotonic stimulation. Cation channel-mediated depolarization was followed by a hyperpolarization mediated by K + channels. The latter was inhibited by l-methionine (TREK1 channel inhibitor) and l-NNA (nitric oxide synthase inhibitor). Correspondingly, mechanical stimulation activated opposing cation and TREK1 currents. NOS inhibition decreased TREK1 currents and potentiated jejunal afferent nerve firing induced by mechanical stimuli. This study suggested a novel activation mechanism of ion channels underlying adaptation under mechanical distension in vagal afferent neurons. The guts' ability to perceive mechanical stimuli is vital in determining how it responds to food intake. The mechanosensation through ion channels could initiate and control gut function.
Competing Interests: Authors have no conflicts of interest to disclose.
Databáze: MEDLINE