The research plan is designed to test specific hypotheses regarding the pre- and postsynaptic regulation of slow excitatory synaptic behavior of myenteric neurons in culture. Slow excitatory synaptic transmission is a mechanism of neural communication in the enteric nervous system and is likely to participate in the regulation of gut motility. The proposed investigations examine the activity of a unique potassium channel found in myenteric neurons and the ionic mechanisms regulating its activity and will link these responses to intracellular changes in postsynaptic calcium concentration. Furthermore, the pharmacology of and mechanism by which presynaptic nicotinic cholinergic receptors modulate release of slow excitatory neurotransmitters will be explored using similar methods of digital imaging, photometry, and simultaneous recording of synaptic events. There are many disorders of gastrointestinal Motility which may arise directly or indirectly from alterations in enteric neural activity. In human medicine, such disorders include irritable bowel syndrome, ulcerative colitis, idiopathic pseudo-obstruction and diabetic neuropathies. These studies will attempt to study the specific interactions between eneric nerves in a simplified system in which several questions can be addressed, these data will contribute to a specific understanding of eneric neurobiology and may facilitate the development of new treatment modalities of gastrointestinal disorders.
| Schneider, D A; Perrone, M; Galligan, J J (2000) Nicotinic acetylcholine receptors at sites of neurotransmitter release to the guinea pig intestinal circular muscle. J Pharmacol Exp Ther 294:363-9 |
| Surprenant, A; Schneider, D A; Wilson, H L et al. (2000) Functional properties of heteromeric P2X(1/5) receptors expressed in HEK cells and excitatory junction potentials in guinea-pig submucosal arterioles. J Auton Nerv Syst 81:249-63 |
| Schneider, D A; Galligan, J J (2000) Presynaptic nicotinic acetylcholine receptors in the myenteric plexus of guinea pig intestine. Am J Physiol Gastrointest Liver Physiol 279:G528-35 |
