Data from: Ca²⁺ signaling in myenteric interstitial cells of Cajal (ICC-MY) and their role as conditional pacemakers in the colon

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. Ca2+ 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 Ca2+ transients that seldom propagated
between cells. Colonic ICC express ANO1 channels, so
Ca2+ transients likely couple to activation of spontaneous
transient inward currents (STICs) in these cells. The
Ca2+ transients were due to Ca2+ release and blocked by
cyclopiazonic acid (CPA), thapsigargin and caffeine, but unaffected by
tetracaine. Antagonists of L- and T-type Ca2+ channels and
reduction in extracellular Ca2+ had minimal effects on
Ca2+ transients. We reasoned that STICs may not activate
regenerative Ca2+ waves in ICC-MY because voltage-dependent
Ca2+ conductances are largely inactivated at the relatively
depolarized potentials of colonic muscles. We tested the effects of
hyperpolarization with pinacidil, a KATP agonist.
Ca2+ waves were initiated in some ICC-MY networks when muscles
were hyperpolarized, and these events were blocked by a T-type
Ca2+ channel antagonist, NNC 55-0396. Ca2+ 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.