L-type calcium channels in the photoreceptor ribbon synapse: localization and role in plasticity.
Calcium (Ca(2+)) influx through voltage-gated Ca(2+)channels stimulates a variety of neural activities, including process outgrowth, neurotransmission, and synaptic plasticity. In general, L-type channels control Ca(2+) influx into the soma and dendrites, whereas other Ca(2+) channel types control presynaptic activities. Neurons that make ribbon synapses, however, are among a select group of nerve cells whose presynaptic Ca(2+)-dependent secretion is linked to L-type channels. Recently, photoreceptor ribbon synapses have been shown to be capable of dramatic structural remodeling and neuritic outgrowth. Here, we have examined 1) the distribution of dihydropyridine (DHP)-sensitive (L-type) Ca(2+) channels in photoreceptor presynaptic structures and 2) the role of these channels in axonal plasticity and process outgrowth in culture. Using anti-alpha(1C) and the fluorescent dihydropyridine, (-)-DM-BODIPY DHP, L-type channels were localized in the outer plexiform layer of retinal sections and in presynaptic terminals of freshly isolated photoreceptors. In the rod terminal, dense patches of label were present; their distribution and number matched that of synaptic ribbons. After 1-7 days in vitro, punctate alpha(1C) staining occurred along newly formed neurites and presynaptic varicosities. Functional channels were present throughout the culture period, as determined by fura-2 imaging. Channel blockage by nicardipine, a DHP antagonist, inhibited axonal remodeling. Specifically, it prevented axon retraction and lamellipodium formation, reduced neurite growth, and produced long, thin processes on some, primarily cone, photoreceptors. L-type Ca(2+) channel activity, therefore, not only stimulates neurotransmission but contributes to presynaptic structural plasticity at the ribbon synapse.
Nachman-Clewner
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M
Graduate Program in Neuroscience, Joan and Sanford I. Weill Graduate School of Medical Sciences of Cornell University, New York, New York 10027, USA.
St Jules
R
R
Townes-Anderson
E
E
D000557:Ambystoma; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000502:physiology*; D002478:Cells, Cultured; D066298:In Vitro Techniques; D018613:Microscopy, Confocal; D016501:Neurites / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology*; D009529:Nicardipine / Q000494:pharmacology; D020419:Photoreceptor Cells, Vertebrate / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000166:cytology / Q000502:physiology; D017949:Retinal Cone Photoreceptor Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D017948:Retinal Rod Photoreceptor Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D013569:Synapses / Q000502:physiology*
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D009529:Nicardipine