Photoreceptor calcium channels: insight from night blindness.
The genetic locus for incomplete congenital stationary night blindness (CSNB2) has been identified as the CACNA1f gene, encoding the alpha 1F calcium channel subunit, a member of the L-type family of calcium channels. The electroretinogram associated with CSNB2 implicates alpha 1F in synaptic transmission between retinal photoreceptors and bipolar cells. Using a recently developed monoclonal antibody to alpha 1F, we localize the channel to ribbon active zones in rod photoreceptor terminals of the mouse retina, supporting a role for alpha 1F in mediating glutamate release from rods. Detergent extraction experiments indicate that alpha 1F is part of a detergent-resistant active zone complex, which also includes the synaptic ribbons. Comparison of native mouse rod calcium currents with recombinant alpha 1F currents reveals that the current-voltage relationship for the native current is shifted approximately 30 mV to more hyperpolarized potentials than for the recombinant alpha 1F current, suggesting modulation of the native channel by intracellular factors. Lastly, we present evidence for L-type alpha 1D calcium channel subunits in cone terminals of the mouse retina. The presence of alpha 1D channels in cones may explain the residual visual abilities of individuals with CSNB2.
Morgans
Catherine W
CW
Neurological Sciences Institute, Oregon Health and Science University, Beaverton, OR 97006, USA. morgansc@ohsu.edu
Bayley
Philippa R
PR
Oesch
Nicholas W
NW
Ren
Gaoying
G
Akileswaran
Lakshmi
L
Taylor
W Rowland
WR
D000429:Alcohol Oxidoreductases; D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015153:Blotting, Western; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D020746:Calcium Channels, L-Type; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004594:Electrophysiology; D007150:Immunohistochemistry; D051379:Mice; D018613:Microscopy, Confocal; D009755:Night Blindness / Q000235:genetics* / Q000503:physiopathology*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D017949:Retinal Cone Photoreceptor Cells / Q000187:drug effects / Q000502:physiology*; D013347:Subcellular Fractions / Q000378:metabolism; D050857:Synaptotagmins / Q000235:genetics / Q000378:metabolism
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; C480684:Cacna1f protein, mouse; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; D010750:Phosphoproteins; D011994:Recombinant Proteins; D050857:Synaptotagmins; D000429:Alcohol Oxidoreductases; C111341:Ctbp2 protein, mouse