Fig. 4.

Functional CSNB2 mutations in Ca_v1.4 α1 cause a decreased dynamic range of photoreceptor signaling: the operation range of photoreceptors (between -35 mV (dark) and approximately -55 mV (light) is near the foot of the I _Ca activation curve at physiological Ca²⁺ concentrations to ensure Ca²⁺ influx necessary for tonic glutamate release (see also text). A hyperpolarizing shift of the current–voltage relationship (I–V) is predicted to result in higher glutamate release at a given illumination level, causing a decreased dynamic range of photoreceptor signaling (here shown for mutation K1591X). According to the L-type current I–V relationship measured in photoreceptors (black curve [80]), a 13-mV hyperpolarizing shift of the I _Ca I–V relationship as observed for K1591X [67] would predict a smaller increase of I _Ca and exocytosis (predicted: normal ∼50-fold, K1591X ∼3-fold) when moving from the light (-55 mV) to the dark membrane potential (-35 mV)