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Abl family kinases regulate neuronal nicotinic receptors and synapses in chick ciliary ganglion neurons

Jayakar, Selwyn S.
http://rave.ohiolink.edu/etdc/view?acc_num=mco1242668863

Abstract Details

2009, Doctor of Philosophy in Biomedical Sciences (Ph.D.), University of Toledo, College of Medicine.
Nicotinic acetylcholine receptors (nAChRs) mediate fast excitatory synaptictransmission at neuronal nicotinic synapses in the autonomic nervous system and regulate synaptic transmission by modulating presynaptic vesicle release, in the brain. Their wide distribution and function link nicotinic synapses and nAChRs to several neurological and immunological disorders. Hence molecules that regulate nicotinic synaptic function and nAChRs are attractive therapeutic candidates. Abl family non-receptor tyrosine kinases (AFKs) have been shown to contribute to synaptic function and development. AFKs facilitate agrin-mediated clustering of nAChRs in developing muscle cells by mediating downstream tyrosine phosphorylation. Also, AFKs expressed in mature hippocampal synapses modulate synaptic efficacy. However the role of AFKs in regulating nicotinic synapses is unknown. Here we investigate the role of AFKs in regulating neuronal nicotinic synapses in chick ciliary ganglion (cCG) neurons and show that AFKs regulate nicotinic synapses by modulating postsynaptic nAChR function without affecting nAChR surface clusters. Inhibiting AFK kinase activity using STI571 concurrently decreases basal levels of synaptic activity by decreasing quantal size and down-regulating whole-cell nAChR responses. Unlike the developing muscle, inhibition of AFK activity was not associated with the dispersion of nAChR surface clusters. However, the effects of STI571 were specific to nAChRs, non-competitive at the nicotine-binding site and did not involve open channel blockade. These studies show that AFK activity may sustain basal nicotinic synaptic function by regulating postsynaptic nAChR functional activity; however, AFK activity may not contribute to the stability of postsynaptic nAChR clusters.
Joseph Margiotta, Ph.D. (Committee Chair)
Marthe Howard, Ph.D. (Committee Member)
David Giovannucci, Ph.D. (Committee Member)
Linda Dokas, Ph.D. (Committee Member)
John Wall, Ph.D. (Committee Member)
153 p.
Neurology
Nicotinic Receptors; ABL Kinase; Ciliary Ganglion; Quantal Analysis; Confocal; Patch Clamp

Recommended Citations

Citations

  • Jayakar, S. S. (2009). Abl family kinases regulate neuronal nicotinic receptors and synapses in chick ciliary ganglion neurons [Doctoral dissertation, University of Toledo]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=mco1242668863

    APA Style (7th edition)

  • Jayakar, Selwyn. Abl family kinases regulate neuronal nicotinic receptors and synapses in chick ciliary ganglion neurons. 2009. University of Toledo, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=mco1242668863.

    MLA Style (8th edition)

  • Jayakar, Selwyn. "Abl family kinases regulate neuronal nicotinic receptors and synapses in chick ciliary ganglion neurons." Doctoral dissertation, University of Toledo, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=mco1242668863

    Chicago Manual of Style (17th edition)

mco1242668863
494
© 2009, some rights reserved.Creative Commons License Abl family kinases regulate neuronal nicotinic receptors and synapses in chick ciliary ganglion neurons by Selwyn S. Jayakar is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. Based on a work at etd.ohiolink.edu.
This open access ETD is published by University of Toledo Health Science Campus and OhioLINK.