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J Biol Chem, Vol. 273, Issue 29, 18308-18315, July 17, 1998
Promotion and Inhibition of L-type Ca2+
Channel Facilitation by Distinct Domains of the Subunit
Thierry
Cens,
Sophie
Restituito,
Alice
Vallentin, and
Pierre
Charnet
From the Centre de Recherche de Biochimie Macromoléculaire,
CNRS Unité Propre de Recherche 1086, 1919 Route de Mende, BP
5051, F34033 Montpellier, France
Ca2+ current potentiation by
conditioning depolarization is a general mechanism by which excitable
cells can control the level of Ca2+ entry during repetitive
depolarizations. Several types of Ca2+ channels are
sensitive to conditioning depolarization, however, using clearly
distinguishable mechanisms. In the case of L-type Ca2+ channels, prepulse-induced current facilitation can
only be recorded when the pore-forming 1C subunit is
coexpressed with the auxiliary 1, 3, or
4, but not 2, subunit. These four subunits are composed of two conserved domains surrounded by central,
N-terminal, and C-terminal variable regions. Using different deleted
and chimeric forms of the 1 and 2
subunits, we have mapped essential sequences for L-type
Ca2+ channel facilitation. A first sequence, located in the
second conserved domain of all subunits, is responsible for the
promotion of current facilitation by the subunit. A second sequence
of 16 amino acids, located on the N-terminal tail of the
2 subunit, induces a transferable block of
L-type current facilitation. Site-specific mutations reveal
the essential inhibitory role played by three positive charges on this
segment. The lack of prepulse-induced current facilitation recorded
with some truncated forms of the 2 subunit suggests the
existence of an additional inhibitory sequence in the 2
subunit.
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.

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Copyright © 1998 by the American Society for Biochemistry and Molecular Biology.
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