P/Q and N channels control baseline and spike-triggered calcium levels in neocortical axons and synaptic boutons.
Cortical axons contain a diverse range of voltage-activated ion channels, including Ca(2+) currents. Interestingly, Ca(2+) channels are not only located at presynaptic terminals, but also in the axon initial segment (AIS), suggesting a potentially important role in the regulation of action potential generation and neuronal excitability. Here, using two-photon microscopy and whole-cell patch-clamp recording, we examined the properties and role of calcium channels located in the AIS and presynaptic terminals of ferret layer 5 prefrontal cortical pyramidal cells in vitro. Subthreshold depolarization of the soma resulted in an increase in baseline and spike-triggered calcium concentration in both the AIS and nearby synaptic terminals. The increase in baseline calcium concentration rose with depolarization and fell with hyperpolarization with a time constant of approximately 1 s and was blocked by removal of Ca(2+) from the bathing medium. The increases in calcium concentration at the AIS evoked by subthreshold or suprathreshold depolarization of the soma were blocked by the P/Q-channel antagonist omega-agatoxin IVA or the N-channel antagonist omega-conotoxin GVIA or both. The presence of these channels in the AIS pyramidal cells was confirmed with immunochemistry. Block of these channels slowed axonal action potential repolarization, apparently from reduction of the activation of a Ca(2+)-activated K(+) current, and increased neuronal excitability. These results demonstrate novel mechanisms by which calcium currents may control the electrophysiological properties of axonal spike generation and neurotransmitter release in the neocortex.
Yu
Yuguo
Y
Department of Neurobiology, Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Maureira
Carlos
C
Liu
Xiuxin
X
McCormick
David
D
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001369:Axons / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D020864:Calcium Channels, N-Type / Q000502:physiology*; D020865:Calcium Channels, P-Type / Q000502:physiology*; D020907:Calcium Channels, Q-Type / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology*; D005260:Female; D005289:Ferrets; D008297:Male; D019579:Neocortex / Q000166:cytology / Q000502:physiology*; D017729:Presynaptic Terminals / Q000502:physiology*
D020864:Calcium Channels, N-Type; D020865:Calcium Channels, P-Type; D020907:Calcium Channels, Q-Type; D002118:Calcium
J Neurosci. 2006 Feb 8;26(6):1854-63
16467534
J Neurosci. 2006 Jun 28;26(26):7071-81
16807336
J Physiol. 2004 May 15;557(Pt 1):147-57
15034127
J Physiol. 1999 Nov 15;521 Pt 1:135-46
10562340
Neuroscientist. 2006 Aug;12(4):317-26
16840708
J Pharmacol Exp Ther. 2000 Oct;295(1):302-8
10991994
J Physiol. 2007 May 1;580(Pt.3):859-82
17303637
J Neurophysiol. 1995 Sep;74(3):1335-42
7500154
Trends Neurosci. 1996 Apr;19(4):150-4
8658599
Mol Pharmacol. 2006 Jun;69(6):1963-8
16510561
J Neurosci. 2003 May 1;23(9):3639-48
12736335
J Neurosci. 2008 Jul 16;28(29):7260-72
18632930
J Neurosci. 2007 Jul 25;27(30):7888-98
17652580
Nature. 2010 Jun 24;465(7301):1070-4
20543823
Nat Neurosci. 2009 Aug;12(8):996-1002
19633666
J Pharmacol Exp Ther. 2004 Apr;309(1):193-9
14718587
Eur J Pharmacol. 2003 Aug 15;475(1-3):11-8
12954354
Neuron. 2003 Sep 11;39(6):961-73
12971896
Neuron. 2005 Oct 6;48(1):109-21
16202712
J Neurosci. 2007 May 30;27(22):5903-14
17537961
J Neurosci. 2006 Mar 29;26(13):3465-73
16571753
J Neurosci. 2003 Jun 1;23(11):4509-18
12805291
J Neurosci. 2006 Mar 8;26(10):2599-613
16525039
Nat Rev Neurosci. 2004 Apr;5(4):304-16
15034555
J Biol Chem. 1990 Jul 5;265(19):11083-90
1694175
J Neurosci. 2004 Feb 4;24(5):1236-44
14762142
Cereb Cortex. 2005 Feb;15(2):152-65
15238439
Nature. 2006 Jun 8;441(7094):761-5
16625207
J Neurosci. 2008 Nov 12;28(46):11768-77
19005038
Biophys J. 2000 May;78(5):2655-67
10777761
Neuroscience. 1999;92(2):773-82
10408625
Eur J Neurosci. 2002 Oct;16(7):1214-22
12405981
J Neurosci. 2008 Dec 31;28(53):14329-40
19118165
Sci STKE. 2004 Feb 03;2004(219):pl5
14872098
Trends Neurosci. 1997 Mar;20(3):125-31
9061867
Proc Natl Acad Sci U S A. 2007 Jul 3;104(27):11453-8
17581873
J Physiol. 2006 Oct 1;576(Pt 1):235-56
16840518
Science. 2006 Mar 3;311(5765):1290-3
16513983
Nat Neurosci. 2008 Feb;11(2):178-86
18204443
Neuron. 2008 Sep 25;59(6):902-13
18817730
Proc Natl Acad Sci U S A. 2006 Feb 21;103(8):2920-5
16473933
Pflugers Arch. 2009 Mar;457(5):1133-45
18762971
J Neurosci. 2001 Dec 15;21(24):9585-97
11739569
J Physiol. 2000 Dec 15;529 Pt 3:625-46
11118494
J Neurophysiol. 2007 Jan;97(1):746-60
17093120
J Neurosci. 1997 Jun 15;17(12):4570-9
9169518
J Neuroimmunol. 2008 Sep 15;201-202:136-44
18678414
J Physiol. 1995 Aug 15;487(1):67-90
7473260
Neuron. 2009 Jan 29;61(2):259-71
19186168
J Physiol. 2002 Aug 1;542(Pt 3):843-54
12154183
J Neurosci. 2004 Sep 29;24(39):8441-53
15456817
J Membr Biol. 1996 May;151(1):77-90
8661496
Neuron. 2007 Aug 16;55(4):633-47
17698015
J Neurosci. 2008 Jul 30;28(31):7765-73
18667608
Pflugers Arch. 2000 Dec;441(2-3):398-408
11211128