THE ROLE OF INTRACELLULAR SODIUM (Na) IN THE REGULATION OF CALCIUM (Ca)-MEDIATED SIGNALING AND TOXICITY.
It is known that activated N-methyl-D-aspartate receptors (NMDARs) are a major route of excessive calcium ion (Ca(2+)) entry in central neurons, which may activate degradative processes and thereby cause cell death. Therefore, NMDARs are now recognized to play a key role in the development of many diseases associated with injuries to the central nervous system (CNS). However, it remains a mystery how NMDAR activity is recruited in the cellular processes leading to excitotoxicity and how NMDAR activity can be controlled at a physiological level. The sodium ion (Na(+)) is the major cation in extracellular space. With its entry into the cell, Na(+) can act as a critical intracellular second messenger that regulates many cellular functions. Recent data have shown that intracellular Na(+) can be an important signaling factor underlying the up-regulation of NMDARs. While Ca(2+) influx during the activation of NMDARs down-regulates NMDAR activity, Na(+) influx provides an essential positive feedback mechanism to overcome Ca(2+)-induced inhibition and thereby potentiate both NMDAR activity and inward Ca(2+) flow. Extensive investigations have been conducted to clarify mechanisms underlying Ca(2+)-mediated signaling. This review focuses on the roles of Na(+) in the regulation of Ca(2+)-mediated NMDAR signaling and toxicity.
Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, Florida, 32306-4300, USA.
Xian-Min
XM
Yu
Bradley R
BR
Groveman
Xiao-Qian
XQ
Fang
Shuang-Xiu
SX
Lin
Exp Brain Res. 1986;65(1):1-10
3026832
Nature. 1994 May 19;369(6477):235-9
7514273
Biochim Biophys Acta. 2009 Nov;1787(11):1395-401
19576166
Stroke. 2002 Jul;33(7):1882-8
12105370
J Mol Med (Berl). 2000;78(1):3-13
10759025
Crit Rev Biochem Mol Biol. 2001 Apr;36(2):107-260
11370791
J Gen Physiol. 1992 Dec;100(6):933-61
1484286
Nature. 1983 Aug 18-24;304(5927):645-8
6410286
Trends Neurosci. 2005 Aug;28(8):422-8
15979166
Exp Neurol. 2004 Aug;188(2):365-77
15246836
J Neurosci. 1996 Jan 15;16(2):545-52
8551338
Soc Gen Physiol Ser. 1997;52:163-75
9210228
Mol Pharmacol. 1986 Aug;30(2):90-5
3016504
J Neurochem. 1984 Nov;43(5):1369-74
6149259
Prog Brain Res. 1993;96:137-43
8392738
Spine (Phila Pa 1976). 1995 Oct 15;20(20):2187-91
8545710
J Physiol. 1996 Jun 1;493 ( Pt 2):457-70
8782109
Subcell Biochem. 2007;45:481-506
18193649
Physiol Rev. 1994 Jul;74(3):723-60
8036251
Trends Pharmacol Sci. 1990 Nov;11(11):462-8
1980041
J Neurosurg. 1992 Jan;76(1):72-80
1727172
J Physiol. 1996 Sep 1;495 ( Pt 2):449-63
8887756
Ann N Y Acad Sci. 1996 Apr 15;779:300-17
8659844
Nature. 2005 Sep 8;437(7056):215-23
16041361
Annu Rev Physiol. 2001;63:871-94
11181979
J Alzheimers Dis. 2004 Dec;6(6 Suppl):S61-74
15665416
Ann Thorac Surg. 2003 Feb;75(2):S700-8
12607715
Neuron. 2003 Jan 23;37(2):287-97
12546823
J Neurosci. 1999 Feb 15;19(4):1165-78
9952395
Cell. 1996 Mar 8;84(5):745-55
8625412
Cell Calcium. 1998 Feb-Mar;23(2-3):131-4
9601608
Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12458-62
7809059
Pharmacol Rev. 2003 Dec;55(4):575-8
14657413
Pharmacol Rev. 1999 Mar;51(1):7-61
10049997
J Exp Biol. 1986 Sep;124:359-73
2428906
Science. 1997 Jan 31;275(5300):674-8
9005855
Biochem J. 1999 Jul 15;341 ( Pt 2):233-49
10393078
Trends Neurosci. 2006 Apr;29(4):207-15
16494954
J Neurotrauma. 2000 Oct;17(10):801-10
11063049
J Biol Chem. 1995 Sep 22;270(38):22089-92
7673182
J Neurosci. 1994 May;14(5 Pt 1):2585-93
7910200
Neuroscience. 2004;126(1):31-44
15145071
J Neurotrauma. 2000 Oct;17(10):857-69
11063053
Prog Neurobiol. 1987;28(3):197-276
2883706
J Biol Chem. 2003 Oct 3;278(40):39176-84
12821680
Exp Brain Res. 1995;104(3):462-6
7589297
Neurosurgery. 1996 Jun;38(6):1176-95
8727150
J Pharmacol Exp Ther. 2005 Sep;314(3):961-71
15901795
FASEB J. 1995 Feb;9(2):219-28
7781924
Nat Rev Neurosci. 2001 Jun;2(6):397-407
11389473
Nat Rev Neurosci. 2004 Jul;5(7):553-64
15208697
J Neurosci. 1993 Aug;13(8):3612-27
7688041
J Neurosci. 2003 Dec 17;23(37):11681-91
14684870
Biophys J. 1997 May;72(5):2103-16
9129812
J Neurosci. 2005 Oct 26;25(43):9960-7
16251444
Prog Brain Res. 2002;137:177-90
12440368
Nature. 1994 Jun 9;369(6480):486-8
7515479
Nat Rev Mol Cell Biol. 2000 Oct;1(1):11-21
11413485
J Neurosci. 1997 Jun 1;17(11):4359-66
9151752
Cell Calcium. 2002 Nov-Dec;32(5-6):393-404
12543098
Exp Toxicol Pathol. 1999 Feb;51(2):143-50
10192583
Toxicology. 2002 Jul 15;176(3):195-207
12093616
EMBO J. 1998 Jul 15;17(14):3931-9
9670010
J Neurosurg. 1993 Sep;79(3):369-72
8103092
J Cereb Blood Flow Metab. 1981;1(2):203-9
7328140
Neuroscientist. 2002 Dec;8(6):532-9
12467375
J Neurosci. 2001 Jun 15;21(12):4207-14
11404406
Neuron. 2003 Mar 6;37(5):727-8
12628162
Brain Res. 2000 Dec 15;886(1-2):5-14
11119683
J Neurosci. 2004 Dec 8;24(49):11057-69
15590922
J Neurosci. 2006 Jun 7;26(23):6337-45
16763042
Prog Brain Res. 2007;161:217-33
17618980
Trends Pharmacol Sci. 1995 Oct;16(10):356-9
7491714
Neuroscience. 2009 Jan 12;158(1):293-300
19041375
Nat Rev Mol Cell Biol. 2003 Jul;4(7):517-29
12838335
J Physiol. 2000 Jul 1;526 Pt 1:81-90
10878101
J Appl Physiol (1985). 2004 Oct;97(4):1470-6
15180978
J Neurosci. 2005 Apr 27;25(17):4279-87
15858054
J Neurosci. 2009 Apr 8;29(14):4498-511
19357275
J Neurochem. 1996 Dec;67(6):2379-89
8931470
Science. 1995 Mar 10;267(5203):1510-2
7878472
Science. 1981 Sep 11;213(4513):1257-9
7268433
Cell. 1995 Jan 27;80(2):259-68
7834745
Cell Calcium. 1998 Nov-Dec;24(5-6):333-43
10091003
Brain Res. 1994 Nov 14;663(2):329-34
7874519
J Neurotrauma. 1997 Feb;14(2):81-8
9069439
J Physiol. 2000 Nov 15;529 Pt 1:57-68
11080251
J Neurochem. 2005 Apr;93(1):171-85
15773917
Trends Neurosci. 1995 Feb;18(2):58-60
7537408
J Neurosci. 2005 Jan 5;25(1):139-48
15634775
Neuron. 2003 Mar 6;37(5):765-73
12628167
Clin Exp Pharmacol Physiol. 1995 Apr;22(4):295-6
7671445
Nature. 1998 Dec 3;396(6710):469-74
9853755
FEBS Lett. 2004 Jun 1;567(1):96-102
15165900
Br J Pharmacol. 2002 Apr;135(7):1733-42
11934814
J Neurotrauma. 2000 Oct;17(10):843-55
11063052
J Physiol. 2007 Oct 15;584(Pt 2):381-7
17690142
J Cell Biol. 1983 Jul;97(1):92-8
6306015
Brain Res. 2004 Oct 15;1023(2):185-92
15374744
Nature. 2006 Dec 14;444(7121):894-8
17167479
J Neurosci. 1997 May 15;17(10):3503-14
9133375
Anesthesiology. 1996 Feb;84(2):256-72
8602655
Proc Natl Acad Sci U S A. 2005 Sep 6;102(36):12706-11
16123128
Eur J Neurosci. 2005 Feb;21(3):622-36
15733081
Annu Rev Pathol. 2006;1:405-34
18039121
Trends Neurosci. 2002 May;25(5):253-9
11972962
Neuron. 1998 Aug;21(2):443-53
9728925
Mol Neurobiol. 2006 Feb;33(1):63-80
16388111
Proc Natl Acad Sci U S A. 1999 Jul 6;96(14):7697-704
10393883
Nature. 1990 Feb 22;343(6260):764-7
2304551
Proc Natl Acad Sci U S A. 1977 Mar;74(3):1287-90
265573
Annu Rev Neurosci. 1987;10:237-67
2436544
Proc Natl Acad Sci U S A. 2002 Dec 10;99(25):15977-82
12461183
Nat Rev Drug Discov. 2006 Feb;5(2):160-70
16424917
Physiol Rev. 1999 Oct;79(4):1431-568
10508238
J Neurosci. 2009 Jul 15;29(28):8946-59
19605632