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J. Wu, A. D. Marmorstein, Jö. Striessnig, N. S. Peachey; Role of Voltage Dependent Calcium Channel 1D Subunits in the ERG Light Peak Pathway. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1521.
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The electroretinogram (ERG) provides a convenient non-invasive means to monitor the functional status of the neural retina and of the retinal pigment epithelium (RPE), an epithelial layer that plays many important roles in maintaining normal retinal function. The RPE generates three major ERG components, the slowest of which is termed the light peak (LP) and is generated on the basal surface. Prior studies indicate a prominent role of voltage dependent calcium channels (VDCCs) in LP generation . First, this component is selectively reduced by nimodipine. Second, the LP is selectively reduced in lethargic mice, which harbor a loss of function mutation in the VDCC ß4 subunit. Here we demonstrate that the CaV1.3 subunit is also involved.
After overnight dark adaptation, mice were anesthetized, the pupils were dilated, and dc-ERGs were recorded from the corneal surface in response to 7-minute duration stimuli, the intensity of which was controlled with neutral density filters . In a separate recording session, strobe flash stimuli were used to evaluate function of rod photoreceptors, the activity of which activates the RPE.
In comparison to WT littermates, LPs of CaV1.3-/- mice were significantly decreased in amplitude. This reduction does not reflect an abnormality in retinal function, as ERG a-waves were normal.
These results demonstrate that LP generation depends upon VDCC activation. This observation, coupled with the finding that mice lacking bestrophin generate normal or larger than normal LPs  indicate the LP is generated by an as-yet unidentified calcium sensitive chloride channel located on the basal membrane of RPE cells. The activity of this channel is modulated by VDCC activity, which is in turn modulated by bestrophin.  Marmorstein et al., J Gen Physiol 2006;127:57  Wu et al., J Neurophysiol 2004;91:1134
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