title: Differential calcium signaling mediated by voltage-gated calcium channels in rat retinal ganglion cells and their unmyelinated axons.
abstract: Aberrant calcium regulation has been implicated as a causative factor in the degeneration of retinal ganglion cells (RGCs) in numerous injury models of optic neuropathy. Since calcium has dual roles in maintaining homeostasis and triggering apoptotic pathways in healthy and injured cells, respectively, investigation of voltage-gated Ca channel (VGCC) regulation as a potential strategy to reduce the loss of RGCs is warranted. The accessibility and structure of the retina provide advantages for the investigation of the mechanisms of calcium signalling in both the somata of ganglion cells as well as their unmyelinated axons. The goal of the present study was to determine the distribution of VGCC subtypes in the cell bodies and axons of ganglion cells in the normal retina and to define their contribution to calcium signals in these cellular compartments. We report L-type Ca channel α1C and α1D subunit immunoreactivity in rat RGC somata and axons. The N-type Ca channel α1B subunit was in RGC somata and axons, while the P/Q-type Ca channel α1A subunit was only in the RGC somata. We patch clamped isolated ganglion cells and biophysically identified T-type Ca channels. Calcium imaging studies of RGCs in wholemounted retinas showed that selective Ca channel antagonists reduced depolarization-evoked calcium signals mediated by L-, N-, P/Q- and T-type Ca channels in the cell bodies but only by L-type Ca channels in the axons. This differential contribution of VGCC subtypes to calcium signals in RGC somata and their axons may provide insight into the development of target-specific strategies to spare the loss of RGCs and their axons following injury.
authors.affiliation: Department of Neurobiology and Jules Stein Eye Institute, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Allison
authors.initials: A
authors.lastname: Sargoy
authors.affiliation: Department of Neurobiology and Jules Stein Eye Institute, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Neurobiology and Jules Stein Eye Institute, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America ; Veterans Administration Greater Los Angeles Healthcare System, Los Angeles, California, United States of America ; Departments of Physiology & Biophysics and Ophthalmology & Visual Sciences, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Steven
authors.initials: S
authors.lastname: Barnes
authors.affiliation: Department of Neurobiology and Jules Stein Eye Institute, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America ; Veterans Administration Greater Los Angeles Healthcare System, Los Angeles, California, United States of America.
authors.forename: Nicholas C
authors.initials: NC
authors.lastname: Brecha
mesh_terms: D000200:Action Potentials; D000595:Amino Acid Sequence; D000818:Animals; D001369:Axons / Q000378:metabolism*; D015220:Calcium Channels / Q000737:chemistry / Q000378:metabolism*; D020013:Calcium Signaling; D005786:Gene Expression Regulation; D008969:Molecular Sequence Data; D036421:Nerve Fibers, Unmyelinated / Q000378:metabolism*; D021381:Protein Transport; D051381:Rats; D012165:Retinal Ganglion Cells / Q000166:cytology*; D013997:Time Factors
chemical_list: D015220:Calcium Channels