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Ca 2+ ‐sensitive regulation of E‐type Ca 2+ channel activity depends on an arginine‐rich region in the cytosolic II–III loop
Author(s) -
Leroy Jérôme,
Pereverzev Alexey,
Vajna Rolf,
Qin Ning,
Pfitzer Gabriele,
Hescheler Jürgen,
Malécot Claire O.,
Schneider Toni,
Klöckner Udo
Publication year - 2003
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.2003.02819.x
Subject(s) - arginine , biophysics , chemistry , hek 293 cells , cytosol , intracellular , protein subunit , ligand gated ion channel , amino acid , biochemistry , ion channel , biology , receptor , enzyme , gene
Ca 2+ ‐dependent regulation of L‐type and P/Q‐type Ca 2+ channel activity is an important mechanism to control Ca 2+ entry into excitable cells. Here we addressed the question whether the activity of E‐type Ca 2+ channels can also be controlled by Ca 2+ . Switching from Ba 2+ to Ca 2+ as charge carrier increased within 50 s, the density of currents observed in HEK‐293 cells expressing a human Ca v 2.3d subunit and slowed down the inactivation kinetics. Furthermore, with Ca 2+ as permeant ion, recovery from inactivation was accelerated, compared to the recovery process recorded under conditions where the accumulation of [Ca 2+ ] i was prevented. In a Ba 2+ containing bath solution the Ca 2+ ‐dependent changes of E‐type channel activity could be induced by dialysing the cells with 1 µ m free [Ca 2+ ] i suggesting that an elevation of [Ca 2+ ] i is responsible for these effects. Deleting 19 amino acids in the intracellular II–III linker (exon 19) as part of an arginine‐rich region, severely impairs the Ca 2+ responsiveness of the expressed channels. Interestingly, deletion of an adjacent homologue arginine‐rich region activates channel activity but now independently from [Ca 2+ ] i . As a positive feedback‐regulation of channel activity this novel activation mechanism might determine specific biological functions of E‐type Ca 2+ channels.