AB310. SPR-37 Cholinergic excitatory motor responses in the colon are mediated through the calcium-activated chloride conductance Ano1

Objective There is a growing body of evidence that gastrointestinal smooth muscle excitability is regulated by several different classes of interstitial cells [interstitial cells of Cajal (ICC) and PDGFRα(+) cells] that are electrically coupled to SMC. Thus, ‘myogenic’ activity results from the integrated behavior of the SMC/ICC/PDGFRα(+) cell (SIP) syncytium. Inputs from excitatory and inhibitory motor neurons are required to produce the complex motor patterns of the gut and coordinate GI motility. Motor neurons innervate these three cell types in the SIP syncytium, and receptors, second messenger pathways, and ion channels in these cells mediate postjunctional responses. Cholinergic neurotransmission in GI muscles from several species has long been thought to be dependent upon activation of a non-selective cation conductance in smooth muscle cells and the molecular candidates for mediating cholinergic excitation have been reported to be the transient receptor protein channels Trpc4 and Trpc6. However, we have shown that cholinergic responses in the GI tract involve ICC and in their absence these motor responses are greatly diminished or absent. We sought to determine the conductance(s) responsible for cholinergic motor responses in the colon.