TY - JOUR T1 - Excitatory Neuronal Responses of Ca<sup>2+</sup> Transients in Interstitial Cells of Cajal in the Small Intestine JF - eneuro JO - eNeuro DO - 10.1523/ENEURO.0080-18.2018 VL - 5 IS - 2 SP - ENEURO.0080-18.2018 AU - Salah A. Baker AU - Bernard T. Drumm AU - Karolina E. Skowronek AU - Benjamin E. Rembetski AU - Lauren E. Peri AU - Grant W. Hennig AU - Brian A. Perrino AU - Kenton M. Sanders Y1 - 2018/03/01 UR - http://www.eneuro.org/content/5/2/ENEURO.0080-18.2018.abstract N2 - Interstitial cells of Cajal (ICC) regulate smooth muscle excitability and motility in the gastrointestinal (GI) tract. ICC in the deep muscular plexus (ICC-DMP) of the small intestine are aligned closely with varicosities of enteric motor neurons and thought to transduce neural responses. ICC-DMP generate Ca2+ transients that activate Ca2+ activated Cl- channels and generate electrophysiological responses. We tested the hypothesis that excitatory neurotransmitters regulate Ca2+ transients in ICC-DMP as a means of regulating intestinal muscles. High-resolution confocal microscopy was used to image Ca2+ transients in ICC-DMP within murine small intestinal muscles with cell-specific expression of GCaMP3. Intrinsic nerves were stimulated by electrical field stimulation (EFS). ICC-DMP exhibited ongoing Ca2+ transients before stimuli were applied. EFS caused initial suppression of Ca2+ transients, followed by escape during sustained stimulation, and large increases in Ca2+ transients after cessation of stimulation. Basal Ca2+ activity and the excitatory phases of Ca2+ responses to EFS were inhibited by atropine and neurokinin 1 receptor (NK1) antagonists, but not by NK2 receptor antagonists. Exogenous ACh and substance P (SP) increased Ca2+ transients, atropine and NK1 antagonists decreased Ca2+ transients. Neurokinins appear to be released spontaneously (tonic excitation) in small intestinal muscles and are the dominant excitatory neurotransmitters. Subcellular regulation of Ca2+ release events in ICC-DMP may be a means by which excitatory neurotransmission organizes intestinal motility patterns. ER -