Intracellular chloride ions regulate the time course of GABA-mediated inhibitory synaptic transmission.
The time-dependent integration of excitatory and inhibitory synaptic currents is an important process for shaping the input-output profiles of individual excitable cells, and therefore the activity of neuronal networks. Here, we show that the decay time course of GABAergic inhibitory synaptic currents is considerably faster when recorded with physiological internal Cl(-) concentrations than with symmetrical Cl(-) solutions. This effect of intracellular Cl(-) is due to a direct modulation of the GABA(A) receptor that is independent of the net direction of current flow through the ion channel. As a consequence, the time window during which GABAergic inhibition can counteract coincident excitatory inputs is much shorter, under physiological conditions, than that previously measured using high internal Cl(-). This is expected to have implications for neuronal network excitability and neurodevelopment, and for our understanding of pathological conditions, such as epilepsy and chronic pain, where intracellular Cl(-) concentrations can be altered.
Houston
Catriona M
CM
Department of Neuroscience, Physiology & Pharmacology, University College London, London, UK.
Bright
Damian P
DP
Sivilotti
Lucia G
LG
Beato
Marco
M
Smart
Trevor G
TG
D000818:Animals; D000831:Animals, Newborn; D002460:Cell Line; D002712:Chlorides / Q000502:physiology*; D006801:Humans; D053444:Inhibitory Postsynaptic Potentials / Q000502:physiology*; D007424:Intracellular Fluid / Q000502:physiology*; D009433:Neural Inhibition / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000502:physiology*; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D002712:Chlorides; D005680:gamma-Aminobutyric Acid
J Neurosci. 2000 Nov 1;20(21):8069-76
11050128
J Physiol. 1979 Dec;297(0):9-45
536927
J Neurosci. 1997 Oct 15;17(20):7626-33
9315884
Science. 1990 Sep 14;249(4974):1303-6
1975955
J Neurosci. 1997 Oct 15;17(20):7662-72
9315888
J Neurosci. 2003 Apr 1;23(7):2618-26
12684447
Nat Neurosci. 2000 Dec;3(12):1256-65
11100146
J Neurosci. 1992 Nov;12(11):4151-72
1331359
Neuron. 1997 Jan;18(1):167-77
9010214
Neuroscience. 1992 Jul;49(1):13-32
1357584
Neuron. 2007 Mar 15;53(6):829-41
17359918
J Comp Neurol. 1995 Aug 14;359(1):154-94
8557845
Nat Rev Neurosci. 2002 Sep;3(9):728-39
12209121
Neuron. 1995 Jul;15(1):181-91
7542462
J Neurosci. 2003 Mar 15;23(6):2019-31
12657660
Nat Neurosci. 2005 Oct;8(10):1319-28
16158066
Pharmacol Ther. 2004 Jun;102(3):195-221
15246246
J Neurosci. 2008 Jul 23;28(30):7574-84
18650335
Nature. 2003 Aug 21;424(6951):938-42
12931188
Cell. 2004 Oct 15;119(2):257-72
15479642
J Physiol. 1987 Apr;385:243-86
2443667
Int Rev Neurobiol. 1995;38:95-138
8537206
Physiol Rev. 2007 Oct;87(4):1215-84
17928584
Neuron. 1994 Jan;12(1):117-26
8292357
J Physiol. 1999 Sep 15;519 Pt 3:693-712
10457084
Neuron. 1993 Aug;11(2):279-89
7688973
Neuron. 1994 Oct;13(4):949-60
7524562
Nat Neurosci. 2009 Jan;12(1):21-3
19029887
J Neurophysiol. 2005 Sep;94(3):2073-85
15987761
Neuron. 2006 Jan 5;49(1):81-94
16387641
J Neurosci. 2003 Nov 19;23(33):10650-61
14627650
Eur J Neurosci. 2007 May;25(9):2726-40
17561840
Nat Neurosci. 2004 May;7(5):525-33
15097992
J Neurosci. 2008 Nov 5;28(45):11454-67
18987182
J Physiol. 1984 Nov;356:551-64
6097677
Trends Neurosci. 1991 Dec;14(12):515-9
1726341
J Physiol. 1979 Jan;286:265-82
35608
J Neurosci. 2007 May 23;27(21):5559-70
17522301
Nature. 1981 Feb 5;289(5797):509-11
6258081
J Pharmacol Toxicol Methods. 2005 May-Jun;51(3):187-200
15862464
Nature. 1981 Jun 4;291(5814):427-9
6264306
Prog Neurobiol. 1994 Mar;42(4):489-537
7522334
J Physiol. 1993 May;464:273-89
8229801
J Neurosci. 2007 Mar 7;27(10):2560-9
17344393
Nature. 1979 Sep 27;281(5729):315-7
551280
J Physiol. 1978 May;278:177-206
671284
J Neurosci. 2007 Sep 12;27(37):9866-73
17855601