title: P/Q and N channels control baseline and spike-triggered calcium levels in neocortical axons and synaptic boutons.
abstract: 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.
authors.affiliation: Department of Neurobiology, Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
authors.forename: Yuguo
authors.initials: Y
authors.lastname: Yu
authors.forename: Carlos
authors.initials: C
authors.lastname: Maureira
authors.forename: Xiuxin
authors.initials: X
authors.lastname: Liu
authors.forename: David
authors.initials: D
authors.lastname: McCormick
mesh_terms: 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*
chemical_list: D020864:Calcium Channels, N-Type; D020865:Calcium Channels, P-Type; D020907:Calcium Channels, Q-Type; D002118:Calcium
references.citation: J Neurosci. 2006 Feb 8;26(6):1854-63
references.pmid: 16467534
references.citation: J Neurosci. 2006 Jun 28;26(26):7071-81
references.pmid: 16807336
references.citation: J Physiol. 2004 May 15;557(Pt 1):147-57
references.pmid: 15034127
references.citation: J Physiol. 1999 Nov 15;521 Pt 1:135-46
references.pmid: 10562340
references.citation: Neuroscientist. 2006 Aug;12(4):317-26
references.pmid: 16840708
references.citation: J Pharmacol Exp Ther. 2000 Oct;295(1):302-8
references.pmid: 10991994
references.citation: J Physiol. 2007 May 1;580(Pt.3):859-82
references.pmid: 17303637
references.citation: J Neurophysiol. 1995 Sep;74(3):1335-42
references.pmid: 7500154
references.citation: Trends Neurosci. 1996 Apr;19(4):150-4
references.pmid: 8658599
references.citation: Mol Pharmacol. 2006 Jun;69(6):1963-8
references.pmid: 16510561
references.citation: J Neurosci. 2003 May 1;23(9):3639-48
references.pmid: 12736335
references.citation: J Neurosci. 2008 Jul 16;28(29):7260-72
references.pmid: 18632930
references.citation: J Neurosci. 2007 Jul 25;27(30):7888-98
references.pmid: 17652580
references.citation: Nature. 2010 Jun 24;465(7301):1070-4
references.pmid: 20543823
references.citation: Nat Neurosci. 2009 Aug;12(8):996-1002
references.pmid: 19633666
references.citation: J Pharmacol Exp Ther. 2004 Apr;309(1):193-9
references.pmid: 14718587
references.citation: Eur J Pharmacol. 2003 Aug 15;475(1-3):11-8
references.pmid: 12954354
references.citation: Neuron. 2003 Sep 11;39(6):961-73
references.pmid: 12971896
references.citation: Neuron. 2005 Oct 6;48(1):109-21
references.pmid: 16202712
references.citation: J Neurosci. 2007 May 30;27(22):5903-14
references.pmid: 17537961
references.citation: J Neurosci. 2006 Mar 29;26(13):3465-73
references.pmid: 16571753
references.citation: J Neurosci. 2003 Jun 1;23(11):4509-18
references.pmid: 12805291
references.citation: J Neurosci. 2006 Mar 8;26(10):2599-613
references.pmid: 16525039
references.citation: Nat Rev Neurosci. 2004 Apr;5(4):304-16
references.pmid: 15034555
references.citation: J Biol Chem. 1990 Jul 5;265(19):11083-90
references.pmid: 1694175
references.citation: J Neurosci. 2004 Feb 4;24(5):1236-44
references.pmid: 14762142
references.citation: Cereb Cortex. 2005 Feb;15(2):152-65
references.pmid: 15238439
references.citation: Nature. 2006 Jun 8;441(7094):761-5
references.pmid: 16625207
references.citation: J Neurosci. 2008 Nov 12;28(46):11768-77
references.pmid: 19005038
references.citation: Biophys J. 2000 May;78(5):2655-67
references.pmid: 10777761
references.citation: Neuroscience. 1999;92(2):773-82
references.pmid: 10408625
references.citation: Eur J Neurosci. 2002 Oct;16(7):1214-22
references.pmid: 12405981
references.citation: J Neurosci. 2008 Dec 31;28(53):14329-40
references.pmid: 19118165
references.citation: Sci STKE. 2004 Feb 03;2004(219):pl5
references.pmid: 14872098
references.citation: Trends Neurosci. 1997 Mar;20(3):125-31
references.pmid: 9061867
references.citation: Proc Natl Acad Sci U S A. 2007 Jul 3;104(27):11453-8
references.pmid: 17581873
references.citation: J Physiol. 2006 Oct 1;576(Pt 1):235-56
references.pmid: 16840518
references.citation: Science. 2006 Mar 3;311(5765):1290-3
references.pmid: 16513983
references.citation: Nat Neurosci. 2008 Feb;11(2):178-86
references.pmid: 18204443
references.citation: Neuron. 2008 Sep 25;59(6):902-13
references.pmid: 18817730
references.citation: Proc Natl Acad Sci U S A. 2006 Feb 21;103(8):2920-5
references.pmid: 16473933
references.citation: Pflugers Arch. 2009 Mar;457(5):1133-45
references.pmid: 18762971
references.citation: J Neurosci. 2001 Dec 15;21(24):9585-97
references.pmid: 11739569
references.citation: J Physiol. 2000 Dec 15;529 Pt 3:625-46
references.pmid: 11118494
references.citation: J Neurophysiol. 2007 Jan;97(1):746-60
references.pmid: 17093120
references.citation: J Neurosci. 1997 Jun 15;17(12):4570-9
references.pmid: 9169518
references.citation: J Neuroimmunol. 2008 Sep 15;201-202:136-44
references.pmid: 18678414
references.citation: J Physiol. 1995 Aug 15;487(1):67-90
references.pmid: 7473260
references.citation: Neuron. 2009 Jan 29;61(2):259-71
references.pmid: 19186168
references.citation: J Physiol. 2002 Aug 1;542(Pt 3):843-54
references.pmid: 12154183
references.citation: J Neurosci. 2004 Sep 29;24(39):8441-53
references.pmid: 15456817
references.citation: J Membr Biol. 1996 May;151(1):77-90
references.pmid: 8661496
references.citation: Neuron. 2007 Aug 16;55(4):633-47
references.pmid: 17698015
references.citation: J Neurosci. 2008 Jul 30;28(31):7765-73
references.pmid: 18667608
references.citation: Pflugers Arch. 2000 Dec;441(2-3):398-408
references.pmid: 11211128