Voltage-dependent calcium channel CaV1.3 subunits regulate the light peak of the electroretinogram.
In response to light, the mouse retinal pigment epithelium (RPE) generates a series of slow changes in potential that are referred to as the c-wave, fast oscillation (FO), and light peak (LP) of the electroretinogram (ERG). The LP is generated by a depolarization of the basolateral RPE plasma membrane by the activation of a calcium-sensitive chloride conductance. We have previously shown that the LP is reduced in both mice and rats by nimodipine, which blocks voltage-dependent calcium channels (VDCCs) and is abnormal in lethargic mice, carrying a null mutation in the calcium channel beta(4) subunit. To define the alpha(1) subunit involved in this process, we examined mice lacking Ca(V)1.3. In comparison with wild-type (WT) control littermates, LPs were reduced in Ca(V)1.3(-/-) mice. This pattern matched closely with that previously noted in lethargic mice, confirming a role for VDCCs in regulating the signaling pathway that culminates in LP generation. These abnormalities do not reflect a defect in rod photoreceptor activity, which provides the input to the RPE to generate the c-wave, FO, and LP, because ERG a-waves were comparable in WT and Ca(V)1.3(-/-) littermates. Our results identify Ca(V)1.3 as the principal pore-forming subunit of VDCCs involved in stimulating the ERG LP.
Wu
Jiang
J
Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Marmorstein
Alan D
AD
Striessnig
Jörg
J
Peachey
Neal S
NS
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D020747:Calcium Channels, T-Type / Q000172:deficiency / Q000502:physiology*; D004307:Dose-Response Relationship, Radiation; D004596:Electroretinography; D005071:Evoked Potentials / Q000502:physiology* / Q000528:radiation effects; D008027:Light; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010775:Photic Stimulation / Q000379:methods
C498197:Cacna1g protein, mouse; D020747:Calcium Channels, T-Type