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