Tetrodotoxin-resistant sodium channels contribute to directional responses in starburst amacrine cells.
The biophysical mechanisms that give rise to direction selectivity in the retina remain uncertain. Current evidence suggests that the directional signal first arises within the dendrites of starburst amacrine cells (SBACs). Two models have been proposed to explain this phenomenon, one based on mutual inhibitory interactions between SBACs, and the other positing an intrinsic dendritic mechanism requiring a voltage-gradient depolarizing towards the dendritic tips. We tested these models by recording current and voltage responses to visual stimuli in SBACs. In agreement with previous work, we found that the excitatory currents in the SBACs were directional, and remained directional when GABA receptors were blocked. Contrary to the mutual-inhibitory model, stimuli that produce strong directional signals in ganglion cells failed to reveal a significant inhibitory input to SBACs. Suppression of the tonic excitatory conductance, proposed to generate the dendritic voltage-gradient required for the dendrite autonomous model, failed to eliminate the directional signal in SBACs. However, selective block of tetrodotoxin-resistant sodium channels did reduce the strength of the directional excitatory signal in the SBACs. These results indicate that current models of direction-selectivity in the SBACs are inadequate, and suggest that voltage-gated excitatory channels, specifically tetrodotoxin-resistant sodium channels, are important elements in directional signaling. This is the first physiological evidence that tetrodotoxin-resistant sodium channels play a role in retinal information processing.
Oesch
Nicholas W
NW
Neuroscience Graduate Program, Oregon Health and Sciences University, Portland, Oregon, United States of America. oeschn@ninds.nih.gov
Taylor
W Rowland
WR
D025042:Amacrine Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D004553:Electric Conductivity; D009038:Motion; D011810:Quinoxalines / Q000494:pharmacology; D011817:Rabbits; D026941:Sodium Channel Blockers / Q000494:pharmacology*; D015222:Sodium Channels / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology*
D011810:Quinoxalines; D026941:Sodium Channel Blockers; D015222:Sodium Channels; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D013779:Tetrodotoxin
J Neurosci. 2002 Dec 15;22(24):10509-13
12486140
Mol Pharmacol. 2002 Sep;62(3):433-8
12181417
Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):16047-52
14665697
J Comp Neurol. 2008 Jun 20;508(6):940-51
18399542
J Neurophysiol. 1997 Feb;77(2):675-89
9065840
Neuron. 2004 Dec 2;44(5):851-64
15572115
Science. 1976 Jan 16;191(4223):204-5
1857
Proc Natl Acad Sci U S A. 1983 May;80(10):3069-73
6574470
J Neurosci. 2004 Aug 18;24(33):7335-43
15317859
Nature. 2002 Aug 22;418(6900):845-52
12192402
J Neurophysiol. 2003 May;89(5):2449-58
12611993
J Neurosci. 2002 Sep 1;22(17):7712-20
12196594
J Neurophysiol. 1996 Jan;75(1):469-80
8822571
J Neurosci. 2001 Jul 1;21(13):4543-50
11425883
Proc Natl Acad Sci U S A. 2006 Dec 5;103(49):18793-8
17124178
J Neurophysiol. 1995 Jul;74(1):12-23
7472316
J Neurochem. 1981 Oct;37(4):867-77
7320727
J Physiol. 1978 Mar;276:277-98
650450
J Neurosci. 1998 Mar 15;18(6):2301-8
9482814
Neuron. 2006 Sep 21;51(6):787-99
16982423
Neuron. 2001 Jun;30(3):771-80
11430810
Vis Neurosci. 1997 Nov-Dec;14(6):1073-88
9447689
Brain Res. 1980 Sep 8;196(2):365-72
6249448
J Physiol. 1993 Apr;463:39-56
8246189
Science. 2000 Sep 29;289(5488):2347-50
11009420
Vis Neurosci. 2002 Jul-Aug;19(4):495-509
12511082
Bull Math Biol. 1992 Nov;54(6):905-28
1515871
J Neurophysiol. 2000 Nov;84(5):2564-71
11067998
Neuron. 2005 Sep 1;47(5):739-50
16129402
Eur J Neurosci. 1995 Nov 1;7(11):2308-21
8563980
Neuron. 2005 Apr 7;46(1):117-27
15820698
Proc Natl Acad Sci U S A. 1995 Feb 14;92(4):1127-31
7862647
PLoS Biol. 2007 Jul;5(7):e185
17622194
J Neurophysiol. 1992 Sep;68(3):711-25
1432044
Vis Neurosci. 2004 Jul-Aug;21(4):611-25
15579224
Vis Neurosci. 2001 Sep-Oct;18(5):799-809
11925015
Nature. 2002 Nov 28;420(6914):411-4
12459782
Nat Neurosci. 2001 Feb;4(2):176-83
11175879
Sci STKE. 2002 Feb 19;2002(120):pl2
11854538
Pflugers Arch. 2005 Dec;451(3):454-63
15981012
J Physiol. 1993 Jul;466:9-37
8410717
J Neurophysiol. 2007 Jun;97(6):4225-34
17428902
J Neurosci. 1994 Nov;14(11 Pt 1):6301-16
7965037
J Neurosci. 1997 May 15;17(10):3503-14
9133375
Vis Neurosci. 1995 Jan-Feb;12(1):177-84
7718498
Proc Natl Acad Sci U S A. 2000 Feb 29;97(5):2326-31
10681444
Trends Neurosci. 1994 Apr;17(4):161-6
7517596
Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):8057-62
8755602
Vis Neurosci. 1999 Mar-Apr;16(2):285-90
10367963
Science. 1992 May 22;256(5060):1202-5
1375397