Ca²⁺ signaling in myenteric interstitial cells of Cajal (ICC-MY) and their role as conditional pacemakers in the colon
Year: 2024
Type: article
Abstract: Interstitial cells of Cajal in the plane of the myenteric plexus (ICC-MY) serve as electrical pacemakers in the stomach and small intestine. A similar population of cells is found in the colon, but these cells do not appear to generate regular slow wave potentials, as characteristic in more proximal gut regions. Ca 2+ handling mechanisms in ICC-MY of the mouse proximal colon were studied using confocal imaging of muscles from animals expressing GCaMP6f exclusively in ICC . ICC-MY displayed stochastic, localized Ca 2+ transients that seldom propagated between cells. Colonic ICC express ANO1 channels, so Ca 2+ transients likely couple to activation of spontaneous transient inward currents (STICs) in these cells. The Ca 2+ transients were due to Ca 2+ release and blocked by cyclopiazonic acid (CPA), thapsigargin and caffeine, but unaffected by tetracaine. Antagonists of L- and T-type Ca 2+ channels and reduction in extracellular Ca 2+ had minimal effects on Ca 2+ transients. We reasoned that STICs may not activate regenerative Ca 2+ waves in ICC-MY because voltage-dependent Ca 2+ conductances are largely inactivated at the relatively depolarized potentials of colonic muscles. We tested the effects of hyperpolarization with pinacidil, a K ATP agonist. Ca 2+ waves were initiated in some ICC-MY networks when muscles were hyperpolarized, and these events were blocked by a T-type Ca 2+ channel antagonist, NNC 55–0396. Ca 2+ waves activated by excitatory nerve stimulation were significantly enhanced by hyperpolarization. Our data suggest that colonic ICC-MY are conditional pacemaker cells that depend upon preparative hyperpolarization, produced physiologically by inputs from enteric inhibitory neurons and necessary for regenerative pacemaker activity.
Source: Cell Calcium
Institutions: University of Nevada, Reno, Dundalk Institute of Technology
Language: English
Subfield: Gastroenterology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,660
OpenAlex ID: W4405842485