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Identification of structural and functional determinants of Ca 2+ ‐dependent kinetics of voltage‐gated calcium channel regulation by CaM
Author(s) -
Taiakina Valentina,
Spafford David,
Guillemette Joseph Guy
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.703.12
Subject(s) - calmodulin , regulator , calcium channel , kinetics , channel (broadcasting) , biophysics , chemistry , voltage dependent calcium channel , electrophysiology , biology , calcium , biochemistry , neuroscience , physics , computer science , gene , telecommunications , organic chemistry , quantum mechanics
Calmodulin (CaM), a widely expressed and highly conserved Ca 2+ ‐sensing regulatory protein with at least 300 known targets, has been recently implicated in the Ca 2+ ‐dependent inactivation and facilitation of voltage‐gated calcium channels. Due to its bi‐lobed structure, CaM is able to serve as a bi‐functional sensor and regulator of channel activity. The particular contribution of each of the two lobes and the associated forms of regulation are not universally understood or generalized for each channel type, and even less so are the particular channel regions responsible for the association and regulation by CaM. In this study we examined unique regions outside the canonical channel CaM‐binding domains for their ability to dictate the electrophysiological profile of any channel type. Channel chimaeras were constructed and patch‐clamp recordings were performed to determine the Ca 2+ ‐dependent kinetics profiles. Furthermore, the peptides corresponding to putative CaM‐binding regions of the channel were synthesized and the binding properties were analyzed. The implications for the channel regulatory model and some unifying principles are discussed. This work received NSERC funding.