Responses to Enteric Motor Neurons in the Gastric Fundus of Mice With Reduced Intramuscular Interstitial Cells of Cajal

Abstract

Background/AimsInterstitial cells of Cajal (ICC) play important functions in motor activity of the gastrointestinal tract. The role of ICC as pacemakers is well established, however their participation in neurotransmission is controversial. Studies using mutant animals that lack ICC have yielded variable conclusions on their importance in enteric motor responses. The purpose of this study was to:(1) clarify the role of intramuscular ICC (ICC-IM) in gastric motor-neurotransmission and (2) ConclusionsThis study demonstrates that ICC-IM mediate nitrergic inhibitory neurotransmission in the fundus and provides evidence of plasticity changes in neuronal responses that may explain discrepancies in previous functional studies which utilized mutant animals to examine the role of ICC-IM in gastric enteric motor responses.

The Significance of Interstitial Cells in Neurogastroenterology

“…Several studies have concluded that ICC-IM are not involved in nitrergic [222][223][224][225] or cholinergic neurotransmission. 222 229 These data support the hypothesis that ICC-IM mediate nitrergic inhibitory neurotransmission in the fundus and may explain the discrepancies in previous functional studies. Some investigators have speculated that NO released from neurons would diffuse freely away from the site of release and it would not be possible to confine NO to a defined neuro-effector junction.…”

The cells and conductance mediating cholinergic neurotransmission in the murine proximal stomach

“…We have also reported that cholinergic neurotrans mission persists in Kit mutants, and contractile responses to cholinergic neurotransmission can actually be enhanced in amplitude vs. responses in wild-type muscles (Sanders et al 2014b). However, assays of post-junctional Ca 2+ sensitization pathways demonstrate that loss of ICC causes recruitment of Ca 2+ sensitization mechanisms that do not appear to be activated by cholinergic neurotransmission in wild-type animals (Bhetwal et al 2013).…”

“…After comparing contractile responses to EFS with the actual lesions in ICC in the muscles under investigation, we more recently found that fundus muscles of W/W V mice are not completely devoid of ICC, as previously assumed (Sanders et al . ). Mice with profound depletion of ICC displayed loss of nitrergic inhibition (1–32 Hz of EFS), although nitrergic responses were maintained in mice retaining portions of the ICC‐IM population.…”

“…However, it was also interesting to note that contractile responses to cholinergic nerve stimulation could be augmented in muscles with reduced ICC populations (Sanders et al . ).…”

“…responses in wild‐type muscles (Sanders et al . ). However, assays of post‐junctional Ca 2+ sensitization pathways demonstrate that loss of ICC causes recruitment of Ca 2+ sensitization mechanisms that do not appear to be activated by cholinergic neurotransmission in wild‐type animals (Bhetwal et al .…”