Nature Neuroscience
- 9, 1108 - 1116 (2006)
Published online: 20 August 2006; | doi:10.1038/nn1751
C-terminal modulator controls Ca2+-dependent gating of Cav1.4 L-type Ca2+ channelsAnamika Singh1, Daniel Hamedinger2, Jean-Charles Hoda1, Mathias Gebhart1, Alexandra Koschak1, Christoph Romanin2 & Jörg Striessnig11
Abteilung Pharmakologie und Toxikologie, Institut für Pharmazie und Centrum für Molekulare Biowissenschaften Innsbruck, Universität Innsbruck, Peter-Mayrstr. 1/I, A-6020 Innsbruck, Austria. 2
Institut für Biophysik, Altenbergerstr. 69, Universität Linz, A-4040 Linz, Austria.
Correspondence should be addressed to Jörg Striessnig joerg.striessnig@uibk.ac.at Tonic neurotransmitter release at sensory cell ribbon synapses is mediated by calcium (Ca2+) influx through L-type voltage-gated Ca2+ channels. This tonic release requires the channels to inactivate slower than in other tissues. Cav1.4 L-type voltage-gated Ca2+ channels (LTCCs) are found at high densities in photoreceptor terminals, and  1 subunit mutations cause human congenital stationary night blindness type-2 (CSNB2). Cav1.4 voltage-dependent inactivation is slow and Ca2+-dependent inactivation (CDI) is absent. We show that removal of the last 55 or 122 (C122) C-terminal amino acid residues of the human 1 subunit restores calmodulin-dependent CDI and shifts voltage of half-maximal activation to more negative potentials. The C terminus must therefore form part of a mechanism that prevents calmodulin-dependent CDI of Cav1.4 and controls voltage-dependent activation. Fluorescence resonance energy transfer experiments in living cells revealed binding of C122 to C-terminal motifs mediating CDI in other Ca2+ channels. The absence of this modulatory mechanism in the CSNB2 truncation mutant K1591X underlines its importance for normal retinal function in humans.
MORE ARTICLES LIKE THIS These links to content published by NPG are automatically generated.
|
