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The α1B Ca 2+ channel amino terminus contributes determinants for β subunit‐mediated voltage‐dependent inactivation properties
Author(s) -
Stephens Gary J.,
Page Karen M.,
Bogdanov Yuri,
Dolphin Annette C.
Publication year - 2000
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.2000.t01-1-00377.x
Subject(s) - protein subunit , amino acid , chemistry , point mutation , serine , cysteine , biophysics , biochemistry , biology , mutation , gene , phosphorylation , enzyme
1 Co‐expression of auxiliary β subunits with the α1B Ca 2+ channel subunit in COS‐7 cells resulted in an increase in current density and a hyperpolarising shift in the mid‐point of activation. Amongst the β subunits, β2a in particular, but also β4 and β1b caused a significant retardation of the voltage‐dependent inactivation compared to currents with α1B alone, whilst no significant changes in inactivation properties were seen for the β3 subunit in this system. 2 Prevention of β2a palmitoylation, by introducing cysteine to serine mutations (β2a(C3,4S)), greatly reduced the ability of β2a to retard voltage‐dependent inactivation. 3 Deletion of the proximal half of the α1B cytoplasmic amino terminus (α1B Δ1‐55 ) differentially affected β subunit‐mediated voltage‐dependent inactivation properties. These effects were prominent with the β2a subunit and, to a lesser extent, with β1b. For β2a, the major effects of this deletion were a partial reversal of β2a‐mediated retardation of inactivation and the introduction of a fast component of inactivation, not seen with full‐length α1B. Deletion of the amino terminus had no other major effects on the measured biophysical properties of α1B when co‐expressed with β subunits. 4 Transfer of the whole α1B amino terminus into α1C (α1bCCCC) conferred a similar retardation of inactivation on α1C when co‐expressed with β2a to that seen in parental α1B. 5 Individual (α1B(Q47A) and α1B(R52A)) and double (α1B(R52,54A)) point mutations within the amino terminus of α1B also opposed the β2a‐mediated retardation of α1B inactivation kinetics. 6 These results indicate that the α1B amino terminus contains determinants for β subunit‐mediated voltage‐dependent inactivation properties. Furthermore, effects were β subunit selective. As deletion of the α1B amino terminus only partially opposed β subunit‐mediated changes in inactivation properties, the amino terminus is likely to contribute to a complex site necessary for complete β subunit function.