Acid-sensing ion channel 2 is important for retinal function and protects against light-induced retinal degeneration

被引:91
作者
Ettaiche, M
Guy, N
Hofman, P
Lazdunski, M
Waldmann, R
机构
[1] CNRS, Inst Pharmacol Mol & Cellulaire, UMR 6097, F-06560 Valbonne, France
[2] Fac Med Nice, INSERM, EPI 02 15, F-06107 Nice, France
关键词
proton-gated channels; ASIC2; vision; rods; acid; neurotransmission; retinal degeneration;
D O I
10.1523/JNEUROSCI.4698-03.2004
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
pH variations in the retina are thought to be involved in the fine-tuning of visual perception. We show that both photoreceptors and neurons of the mouse retina express the H+-gated cation channel subunits acid-sensing ion channel 2a (ASIC2a) and ASIC2b. Inactivation of the ASIC2 gene in mice leads to an increase in the rod electroretinogram a- and b-waves and thus to an enhanced gain of visual transduction. ASIC2 knock-out mice are also more sensitive to light-induced retinal degeneration. We suggest that ASIC2 is a negative modulator of rod phototransduction, and that functional ASIC2 channels are beneficial for the maintenance of retinal integrity.
引用
收藏
页码:1005 / 1012
页数:8
相关论文
共 40 条
[1]   A new member of the acid-sensing ion channel family [J].
Akopian, AN ;
Chen, CC ;
Ding, YN ;
Cesare, P ;
Wood, JN .
NEUROREPORT, 2000, 11 (10) :2217-2222
[2]  
AMES A, 1986, J BIOL CHEM, V261, P3034
[3]   MODULATION OF TRANSMISSION GAIN BY PROTONS AT THE PHOTORECEPTOR OUTPUT SYNAPSE [J].
BARNES, S ;
MERCHANT, V ;
MAHMUD, F .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (21) :10081-10085
[4]   ASIC-like, proton-activated currents in rat hippocampal neurons [J].
Baron, A ;
Waldmann, R ;
Lazdunski, M .
JOURNAL OF PHYSIOLOGY-LONDON, 2002, 539 (02) :485-494
[5]   Zn2+ and H+ are coactivators of acid-sensing ion channels [J].
Baron, A ;
Schaefer, L ;
Lingueglia, E ;
Champigny, G ;
Lazdunski, M .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (38) :35361-35367
[6]  
Benson CJ, 1999, CIRC RES, V84, P921
[7]   Rabbit retinal neurons and glia express a variety of ENaC/DEG subunits [J].
Brockway, LM ;
Zhou, ZH ;
Bubien, JK ;
Jovov, B ;
Benos, DJ ;
Keyser, KT .
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 2002, 283 (01) :C126-C134
[8]   Mutations causing neurodegeneration in Caenorhabditis elegans drastically alter the pH sensitivity and inactivation of the mammalian H+-gated Na+ channel MDEG1 [J].
Champigny, G ;
Voilley, N ;
Waldmann, R ;
Lazdunski, M .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (25) :15418-15422
[9]   A role for ASIC3 in the modulation of high-intensity pain stimuli [J].
Chen, CC ;
Zimmer, A ;
Sun, WH ;
Hall, J ;
Brownstein, MJ ;
Zimmer, A .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (13) :8992-8997
[10]   Exocytosed protons feedback to suppress the Ca2+ current in mammalian cone photoreceptors [J].
DeVries, SH .
NEURON, 2001, 32 (06) :1107-1117