Contribution of Calcium Channel ß Subunits to the Mouse dc–Electroretinogram

Abstract

Abstract: : Purpose: The electroretinogram (ERG) represents the combination of several distinct cellular processes and conductances generated by the neural retina or the retinal pigment epithelium (RPE). Of the latter, the light peak (LP) is known to reflect a Cl conductance across the basal membrane of the RPE. This conductance is thought to be Ca²⁺ sensitive. Since nimodipine, which blocks L–type Ca²⁺ channels, attenuates the LP in rats, we recorded ERGs in mice lacking each of the 4 ß subunits that are critical for correct localization and function of Ca²⁺ channels. Methods: Mice lacking one of the four known Ca²⁺ channel ß subunits have been generated by gene targeting and transgenic rescue (CNS–ß₁, CNS–ß₂), by gene targeting alone (ß₃), or arose spontaneously (lethargic, ß₄ mutant). After overnight dark adaptation, mice were anesthetized with ketamine and xylazine, the pupils were dilated, and an ERG was recorded to a 7–min stimulus. Intensity–response functions were developed from recordings made on separate days. Results: There were no significant differences in any ERG component generated by the RPE in CNS–ß₁, CNS–ß₂ or ß₃ KO mice. In comparison to control littermates, the LP was significantly decreased in lethargic mice. Conclusions: These results are consistent with a model for LP generation that includes a modulatory role of L–type Ca²⁺ channels on a Ca²⁺–sensitive Cl channel that underlies the LP, and implicate the ß₄ subunit as being specifically involved. The unique role of ß₄ in the RPE resembles the role of ß₂ in VDCC–controlled release of glutamate at the photoreceptor–to–bipolar cell synapse (Ball et al., IOVS, 2002;43:1595).

Keywords: electroretinography: non-clinical • retinal pigment epithelium • ion channels