title: A novel analysis of excitatory currents during an action potential from suprachiasmatic nucleus neurons.
abstract: A new application of the action potential (AP) voltage-clamp technique is described based on computational analysis. An experimentally recorded AP is digitized. The resulting Vi vs. ti data set is applied to mathematical models of the ionic conductances underlying excitability for the cell from which the AP was recorded to test model validity. The method is illustrated for APs from suprachiasmatic nucleus (SCN) neurons and the underlying tetrodotoxin-sensitive Na(+) current, INa, and the Ca(2+) current, ICa. Voltage-step recordings have been made for both components from SCN neurons (Jackson et al. 2004). The combination of voltage-step and AP clamp results provides richer constraints for mathematical models of voltage-gated ionic conductances than either set of results alone, in particular the voltage-step results. For SCN neurons the long-term goal of this work is a realistic mathematical model of the SCN AP in which the equations for I(Na) and I(Ca) obtained from this analysis will be a part. Moreover, the method described in this report is general. It can be applied to any excitable cell.
authors.affiliation: National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland.
authors.forename: John R
authors.initials: JR
authors.lastname: Clay
mesh_terms: D000200:Action Potentials; D000818:Animals; D008959:Models, Neurological; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods*; D051381:Rats; D013493:Suprachiasmatic Nucleus / Q000166:cytology / Q000502:physiology*
keywords: action potential clamp; mathematical models; suprachiasmatic nucleus neurons
references.citation: Pflugers Arch. 1989 Apr;413(6):599-603
references.pmid: 2726423
references.citation: Science. 2009 Sep 11;325(5946):1405-8
references.pmid: 19745156
references.citation: Biophys J. 1991 Dec;60(6):1511-33
references.pmid: 1663796
references.citation: J Gen Physiol. 1943 Sep 20;27(1):37-60
references.pmid: 19873371
references.citation: Biophys J. 1991 Dec;60(6):1499-510
references.pmid: 1663795
references.citation: Biophys J. 1985 Sep;48(3):375-90
references.pmid: 2412603
references.citation: Proc Natl Acad Sci U S A. 1982 Apr;79(7):2415-9
references.pmid: 6954549
references.citation: Prog Neurobiol. 2012 Jan;96(1):1-31
references.pmid: 22008116
references.citation: J Gen Physiol. 1997 May;109(5):647-73
references.pmid: 9154910
references.citation: Nat Rev Neurosci. 2007 Jun;8(6):451-65
references.pmid: 17514198
references.citation: J Neurophysiol. 2006 Sep;96(3):1237-46
references.pmid: 16554507
references.citation: J Neurophysiol. 1993 Oct;70(4):1692-703
references.pmid: 7904302
references.citation: Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11806-10
references.pmid: 8265630
references.citation: J Physiol. 2006 Oct 15;576(Pt 2):349-59
references.pmid: 16873403
references.citation: Physiology (Bethesda). 2006 Jun;21:197-207
references.pmid: 16714478
references.citation: Neuron. 2009 Dec 24;64(6):898-909
references.pmid: 20064395
references.citation: Circ Res. 1994 Jun;74(6):1071-96
references.pmid: 7514509
references.citation: J Physiol. 1995 Oct 15;488 ( Pt 2):339-50
references.pmid: 8568674
references.citation: Am J Physiol Heart Circ Physiol. 2002 Feb;282(2):H516-30
references.pmid: 11788399
references.citation: Biophys J. 2008 Jul;95(1):66-87
references.pmid: 18375511
references.citation: Proc R Soc Lond B Biol Sci. 1982 Dec 22;217(1206):101-10
references.pmid: 6131420
references.citation: Nat Neurosci. 2005 May;8(5):650-6
references.pmid: 15852012
references.citation: J Physiol. 1991 Jun;437:27-48
references.pmid: 1653853
references.citation: J Neurosci. 2004 Sep 15;24(37):7985-98
references.pmid: 15371499
references.citation: Neuron. 2005 Feb 3;45(3):405-17
references.pmid: 15694327
references.citation: J Biol Rhythms. 2007 Oct;22(5):445-53
references.pmid: 17876065
references.citation: J Neurophysiol. 2005 Feb;93(2):723-33
references.pmid: 15653786
references.citation: J Physiol. 1949 Mar 1;108(1):37-77
references.pmid: 18128147
references.citation: Front Cell Neurosci. 2009 Dec 23;3:20
references.pmid: 20057933
references.citation: PLoS Comput Biol. 2010 Jul 01;6:e1000840
references.pmid: 20617202
references.citation: Prog Biophys Mol Biol. 2013 Jan;111(1):1-7
references.pmid: 22922062
references.citation: J Physiol. 1952 Aug;117(4):500-44
references.pmid: 12991237
references.citation: J Neurophysiol. 2010 Feb;103(2):632-40
references.pmid: 19939959