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The Journal of Neuroscience, August 15, 2002, 22(16):7065-7079

Regulation of Structural Plasticity by Different Channel Types in Rod and Cone Photoreceptors

Nan Zhang and Ellen Townes-Anderson

Department of Neurosciences, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, New Jersey 07103-2714

In response to retinal disease and injury, the axon terminals of rod photoreceptors demonstrate dramatic structural plasticity, including axonal retraction, neurite extension, and the development of presynaptic varicosities. Cone cell terminals, however, are relatively inactive. Similar events are observed in primary cultures of salamander photoreceptors. To investigate the mechanisms underlying these disparate presynaptic responses, antagonists to voltage-gated L-type and cGMP-gated channels, known to be present on rod and cone cell terminals, respectively, were used to block calcium influx during critical periods of plasticity in vitro. In rod cells, L-type channel antagonists nicardipine and verapamil inhibited not only the outgrowth of processes and the formation of varicosities, but also the synthesis of vesicle proteins, SV2 and synaptophysin. In contrast, the synthesis of opsin in rod cells was unaffected. In cone cells, L-type channel antagonists caused only modest changes. However, cobalt bromide, which blocks all calcium channels, and L-cis-diltiazem, a potent antagonist of cGMP-gated channels, significantly inhibited varicosity formation and synthesis of SV2 in cone cells. Moreover, the cGMP-gated channel agonist 8-bromo-cGMP caused a significant increase in varicosity formation by cone but not rod cells. Thus voltage-gated L-type channels in rod cells and cGMP-gated channels in cone cells are the primary calcium channels required for structural plasticity and the accompanying upregulation of synaptic vesicle synthesis. The differing responses of rod and cone terminals to injury and disease may be determined by these differences in the regulation of Ca2+ influx.

Key words: cone; rod; neuritic process; varicosity; synaptic vesicle proteins; L-type calcium channel; cGMP-gated channel


Copyright © 2002 Society for Neuroscience  0270-6474/02/22167065-15$05.00/0


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