Role of the beta(2) subunit of voltage-dependent calcium channels in the retinal outer plexiform layer.
OBJECTIVE
Mutations in the alpha(1F) subunit of voltage-dependent calcium channels (VDCCs) have been shown to cause incomplete congenital stationary night blindness (CSNB2). The purpose of this study was to dentify which of the four beta subunits of VDCCs participates in the formation of this channel at the photoreceptor synapse and to determine how its absence affects visual processing.


METHODS
Mice without each of the four known beta subunits of VDCCs were generated by gene targeting and transgenic rescue (CNS-beta(1), -beta(2)) or by gene targeting alone (beta(3)) or were obtained from a commercial provider (beta(4)). Retinal function and visual sensitivity were examined by electroretinography and an active avoidance behavioral test, respectively. The structure of the retina and expression of the alpha(1F) subunit were examined at the light microscopic level and by immunohistochemistry.


RESULTS
Under dark-adapted conditions, CNS-beta(2)-null mice had a normal ERG a-wave, but did not have a normal b-wave. In addition, these mice showed decreased sensitivity to light. Both the a- and b-waves appear normal in the CNS-beta(1)-, beta(3)-, and beta(4)-null mice. Histologic analyses of all four mouse lines indicated that only the CNS-beta(2)-null mice had altered retinal morphology. Eyes of these mice had a thinner outer plexiform layer (OPL) than eyes of control animals. In addition, the labeling pattern of the alpha(1F) subunit in the OPL was altered in CNS-beta(2)-null mice.


CONCLUSIONS
The normal distribution of the alpha(1F) subunit of the VDCCs in the OPL is dependent on the expression of the beta(2) subunit. The expression of both of these subunits is required for normal maintenance and/or formation of the OPL and synaptic transmission.
Ball
Sherry L
SL
Research Service, Cleveland VA Medical Center, Cleveland, Ohio, USA.
Powers
Patricia A
PA
Shin
Hee-Sup
HS
Morgans
Catherine W
CW
Peachey
Neal S
NS
Gregg
Ronald G
RG
D000818:Animals; D015153:Blotting, Western; D020746:Calcium Channels, L-Type / Q000502:physiology*; D003623:Dark Adaptation; D004596:Electroretinography; D019084:Fluorescent Antibody Technique, Indirect; D018390:Gene Targeting; D007395:Interneurons / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009755:Night Blindness / Q000151:congenital / Q000235:genetics / Q000378:metabolism*; D010786:Photoreceptor Cells / Q000378:metabolism; D012160:Retina / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology; D014796:Visual Perception / Q000502:physiology
D020746:Calcium Channels, L-Type