Down-regulation of voltage-gated Ca2+ channels by neuronal calcium sensor-1 is beta subunit-specific.
Neuronal Ca(2+) sensor protein-1 (NCS-1) is a member of the Ca(2+) binding protein family, with three functional Ca(2+) binding EF-hands and an N-terminal myristoylation site. NCS-1 is expressed in brain and heart during embryonic and postnatal development. In neurons, NCS-1 facilitates neurotransmitter release, but both inhibition and facilitation of the Ca(2+) current amplitude have been reported. In heart, NCS-1 co-immunoprecipitates with K(+) channels and modulates their activity, but the potential effects of NCS-1 on cardiac Ca(2+) channels have not been investigated. To directly assess the effect of NCS-1 on the various types of Ca(2+) channels we have co-expressed NCS-1 in Xenopus oocytes, with Ca(V)1.2, Ca(V)2.1, and Ca(V)2.2 Ca(2+) channels, using various subunit combinations. The major effect of NCS-1 was to decrease Ca(2+) current amplitude, recorded with the three different types of alpha(1) subunit. When expressed with Ca(V)2.1, the depression of Ca(2+) current amplitude induced by NCS-1 was dependent upon the identity of the beta subunit expressed, with no block recorded without beta subunit or with the beta(3) subunit. Current-voltage and inactivation curves were also slightly modified and displayed a different specificity toward the beta subunits. Taken together, these data suggest that NCS-1 is able to modulate cardiac and neuronal voltage-gated Ca(2+) channels in a beta subunit specific manner.
Rousset
Matthieu
M
Centre de Recherche de Biochimie Macromoléculaire, CNRS Unité Propre de Recherche 1086, Institut Federatif de Recherche 24, 1919 Route de Mende, 34293 Montpellier, France.
Cens
Thierry
T
Gavarini
Sophie
S
Jeromin
Andreas
A
Charnet
Pierre
P
D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000096:biosynthesis / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000096:biosynthesis; D020864:Calcium Channels, N-Type / Q000096:biosynthesis; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D015536:Down-Regulation; D004594:Electrophysiology; D007700:Kinetics; D009206:Myocardium / Q000378:metabolism; D051580:Neuronal Calcium-Sensor Proteins; D009474:Neurons / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism*; D009865:Oocytes / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D014981:Xenopus; D014982:Xenopus laevis
D002118:Calcium; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D002135:Calcium-Binding Proteins; D018076:DNA, Complementary; D051580:Neuronal Calcium-Sensor Proteins; D009479:Neuropeptides; C419385:L-type calcium channel alpha(1C); C101464:frequenin calcium sensor proteins