Channeling Vision: Ca_V1.4—A Critical Link in Retinal Signal Transmission

Figure 3

Mechanisms of C-terminal regulation. (a) In the wild-type channel, with CaM and CaBP4 coexpressed, CaBP4 and the ICDI/CTM competitively interact with the proximal C-terminus, preventing CaM-mediated calcium-dependent inactivation (CDI). (b) When CaBP4 is not present, the ICDI/CTM still competitively inhibits CaM-mediated CDI, but the interaction between the ICDI/CTM and proximal C-terminus causes a significant positive shift in the activation voltage. (c) In the absence of the ICDI/CTM, CaBP4 prevents CDI, and the half-maximal voltage is unaffected, suggesting an additional crucial role for the ICDI/CTM in vivo. (d) The ICDI/CTM can be phosphorylated at serine 1883 by protein kinase A (PKA), allowing CaM to facilitate CDI and modulate channel properties. (e) Overexpression of CaM results in CaM’s outcompeting ICDI/CTM for binding to the proximal C-terminus, thus facilitating CDI. The effect of CaBP4 in this circumstance has yet to be investigated. (f) In the absence of both CaBP4 and the ICDI/CTM, CaM is not competitively inhibited from interaction with the proximal C-terminus; thus, it confers CDI.

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