Calcium sensitive non-selective cation conductances expressed in interstitial cells of Cajal of the gastric antrum

The stomach is an organ within the gastrointestinal tract that plays a critical role in the mechanical breakdown and the initial stages of digestion of ingested foods. The distal portion of the stomach generates electrical slow waves that underlie the rhythmical mechanical activity that mixes and fragments gastric contents. Two distinct populations of interstitial cells of Cajal (ICC) exist within the tunica muscularis of the gastric antrum, and these cells serve distinct physiological functions in this organ. ICC located between the intermuscular plane of the circular and longitudinal muscle layers at the level of the myenteric ICC or ICC-MY generate and actively propagate electrical slow waves. Intramuscular ICC or ICC-IM are dispersed throughout the circular muscle layer and are also excitable, contributing to the waveform of slow waves. ICC-IM also mediate excitatory and inhibitory enteric motor neurotransmission that modulates phasic contraction frequency and force of the gastric antrum. In spite of the key role that ICC plays in gastric excitability, little is known about the ionic conductances that underlie the functional diversity of these cells. In the present thesis, it has been demonstrated, using the patch clamp technique, that the two populations of antral ICC express non-selective cation conductances (NSCC) that exhibit distinct Ca2+ dependencies. One group of ICC-MY-like Kit-positive cells expressed a basal non-selective cation conductance (NSCC) that was inhibited by an increase in [Ca2+]i. The second population of ICC-IM-like Kit-positive cells generated spontaneous transient inward currents (STICs) and expressed a basal noisy NSCC that was facilitated by an increase in [Ca2+]i. It is speculated that the [Ca2+]i inhibited basal NSCC may underlie the pacemaker current in ICC-MY since this basal current shared similar biophysical properties to the pacemaker current described in cultured ICC from the small intestine. On the other hand, prominent STICs were generated by the second population of ICC, which may be responsible for the ongoing discharge of unitary potentials observed in isolated muscle bundles that contain ICC-IM. When [Ca2+]i increases upon cholinergic stimulation or in response to membrane depolarizations driven by pacemaker potentials, the noisy basal currents and STICs may summate into a [Ca 2+]i facilitated current that underlies regenerative potentials in ICC-IM. Upon muscaranic and prostaglandin receptor stimulation, these cells also activate inward current, possibly by the summation of the basal noisy current and STICs and this may be responsible for the active depolarization that occurs with regenerative potentials. In summary, this is the first description of the ionic conductances expressed in distinct populations of ICC in the gastric antrum.