Abstract
Gastrointestinal motility is coordinated by enteric neurons. Both inhibitory and excitatory motor neurons innervate the syncytium consisting of smooth muscle cells (SMCs) interstitial cells of Cajal (ICC) and PDGFRα+ cells (SIP syncytium). Confocal imaging of mouse small intestines from animals expressing GCaMP3 in ICC were used to investigate inhibitory neural regulation of ICC in the deep muscular plexus (ICC-DMP). We hypothesized that Ca2+ signaling in ICC-DMP can be modulated by inhibitory enteric neural input. ICC-DMP lie in close proximity to the varicosities of motor neurons and generate ongoing Ca2+ transients that underlie activation of Ca2+-dependent Cl− channels and regulate the excitability of SMCs in the SIP syncytium. Electrical field stimulation (EFS) caused inhibition of Ca2+ for the first 2–3 s of stimulation, and then Ca2+ transients escaped from inhibition. The NO donor (DEA-NONOate) inhibited Ca2+ transients and Nω-Nitro-L-arginine (L-NNA) or a guanylate cyclase inhibitor (ODQ) blocked inhibition induced by EFS. Purinergic neurotransmission did not affect Ca2+ transients in ICC-DMP. Purinergic neurotransmission elicits hyperpolarization of the SIP syncytium by activation of K+ channels in PDGFRα+ cells. Generalized hyperpolarization of SIP cells by pinacidil (KATP agonist) or MRS2365 (P2Y1 agonist) also had no effect on Ca2+ transients in ICC-DMP. Peptidergic transmitter receptors (VIP and PACAP) are expressed in ICC and can modulate ICC-DMP Ca2+ transients. In summary Ca2+ transients in ICC-DMP are blocked by enteric inhibitory neurotransmission. ICC-DMP lack a voltage-dependent mechanism for regulating Ca2+ release, and this protects Ca2+ handling in ICC-DMP from membrane potential changes in other SIP cells.
Highlights
In the gastrointestinal tract, muscle bundles making up the tunica muscularis have intrinsic mechanisms of excitability, and this has been described as myogenic activity
In the absence of stimulation there was no evidence of coordination between the events occurring within single cells or in other cells within a field-of-vision (FOV), suggesting there was no voltage-dependent regulation of Ca2+ transients in ICC within the deep muscular plexus region (ICCDMP)
Stochastic events occurring in hundreds or thousands of interstitial cells of Cajal (ICC)-DMP could have significant influence on the excitability of cells of the SIP syncytium to which ICCDMP are electrically coupled by abundant gap junctions (Zhou and Komuro, 1992a; Torihashi et al, 1993; Seki and Komuro, 1998)
Summary
Muscle bundles making up the tunica muscularis have intrinsic mechanisms of excitability, and this has been described as myogenic activity. This level of motor control is due to the functions of smooth muscle cells (SMCs), because the behavior of SMCs is modulated by interstitial cells [e.g., interstitial cells of Cajal (ICC) and cells labeled with antibodies to plateletderived growth factor receptor alpha (aka PDGFRα+ cells)]. ICC and PDGFRα+ cells are electrically coupled to SMCs (Zhou and Komuro, 1992a; Torihashi et al, 1993; Seki and Komuro, 1998; Horiguchi and Komuro, 2000), and the resulting cellular network has been referred to as the SIP syncytium (Sanders et al, 2012). Neural inputs are integrated by the SIP syncytium and the output sets the moment-to-moment excitability of the SMCs, generating the underlying basis for motility patterns such as phasic contractions, summation of phasic contractions to generate tone, peristalsis and segmentation
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
