title: Endogenous calcium buffering capacity of substantia nigral dopamine neurons.
abstract: Dopamine (DA)-containing cells from the substantia nigra pars compacta (SNc) play a major role in the initiation of movement. Loss of these cells results in Parkinson's disease (PD). Changes in intracellular calcium ion concentration ([Ca(2+)](i)) elicit several events in DA cells, including spike afterhyperpolarizations (AHPs) and subthreshold oscillations underlying autonomous firing. Continuous Ca(2+) load due to Ca(2+)-dependent rhythmicity has been proposed to cause the death of DA cells in PD and normal aging. Because of the physiological and pathophysiological importance of [Ca(2+)](i) in DA cells, we characterized their intrinsic Ca(2+)-buffering capacity (K(S)) in brain slices. We introduced a fluorescent Ca(2+)-sensitive exogenous buffer (200 microM fura-2) and cells were tracked from break-in until steady state by stimulating with a single action potential (AP) every 30 s and measuring the Ca(2+) transient from the proximal dendrite. DA neurons filled exponentially with a tau of about 5-6 min. [Ca(2+)](i) was assumed to equilibrate between the endogenous Ca(2+) buffer and the exogenous Ca(2+) indicator buffer. Intrinsic buffering was estimated by extrapolating from the linear relationships between the amplitude or time constant of the Ca(2+) transients versus [fura-2]. Extrapolated Ca(2+)-transients in the absence of fura-2 had mean peak amplitudes of 293.7 +/- 65.3 nM and tau = 124 +/- 13 ms (postnatal day 13 [P13] to P17 animals). Intrinsic buffering increased with age in DA neurons. For cells from animals P13-P17, K(S) was estimated to be about 110 (n = 20). In older animals (P25-P32), the estimate was about 179 (n = 10). These relatively low values may reflect the need for rapid Ca(2+) signaling, e.g., to allow activation of sK channels, which shape autonomous oscillations and burst firing. Low intrinsic buffering may also make DA cells vulnerable to Ca(2+)-dependent pathology.
authors.affiliation: Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, University of Tennessee, Memphis, Tennessee 38163, USA. rfoehrin@utmem.edu
authors.forename: R C
authors.initials: RC
authors.lastname: Foehring
authors.forename: X F
authors.initials: XF
authors.lastname: Zhang
authors.forename: J C F
authors.initials: JC
authors.lastname: Lee
authors.forename: J C
authors.initials: JC
authors.lastname: Callaway
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000375:Aging / Q000502:physiology; D000465:Algorithms; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003712:Dendrites / Q000502:physiology; D004298:Dopamine / Q000378:metabolism*; D016257:Fura-2; D066298:In Vitro Techniques; D007700:Kinetics; D016014:Linear Models; D008564:Membrane Potentials / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000502:physiology*
chemical_list: D002118:Calcium; D016257:Fura-2; D004298:Dopamine
references.citation: Brain Res. 1977 Nov 11;136(2):243-60
references.pmid: 922484
references.citation: J Neurophysiol. 1998 Jul;80(1):350-64
references.pmid: 9658056
references.citation: Neuroscience. 1997 Sep;80(2):545-57
references.pmid: 9284356
references.citation: Brain Res. 1990 Sep 3;526(2):303-7
references.pmid: 2257487
references.citation: Brain Res. 1987 Dec 22;437(1):45-55
references.pmid: 3427482
references.citation: Neuron. 2003 Sep 11;39(6):889-909
references.pmid: 12971891
references.citation: J Neurophysiol. 1995 Sep;74(3):1137-48
references.pmid: 7500139
references.citation: Brain Res. 1996 Feb 5;708(1-2):201-4
references.pmid: 8720880
references.citation: J Comput Neurosci. 1998 Jul;5(3):331-48
references.pmid: 9663555
references.citation: Mitochondrion. 2008 Mar;8(2):164-9
references.pmid: 18226984
references.citation: J Neurosci. 1987 Dec;7(12):3935-44
references.pmid: 2891800
references.citation: Exp Brain Res. 1991;86(1):141-50
references.pmid: 1756785
references.citation: J Neurosci Methods. 1991 Feb;36(2-3):253-61
references.pmid: 2062120
references.citation: Neurosci Res. 1993 Dec;18(3):195-207
references.pmid: 7907413
references.citation: J Comp Neurol. 2000 May 22;421(1):107-35
references.pmid: 10813775
references.citation: J Neurosci. 1989 Apr;9(4):1233-41
references.pmid: 2703874
references.citation: J Physiol. 2008 Aug 15;586(16):3795-811
references.pmid: 18591186
references.citation: Trends Neurosci. 1992 Aug;15(8):303-8
references.pmid: 1384200
references.citation: J Neurosci. 1984 Nov;4(11):2866-76
references.pmid: 6150070
references.citation: Nat Rev Neurosci. 2004 Jun;5(6):483-94
references.pmid: 15152198
references.citation: J Neurosci. 2003 Mar 1;23(5):1612-21
references.pmid: 12629165
references.citation: Neuroreport. 1996 Feb 29;7(3):809-14
references.pmid: 8733751
references.citation: J Neurosci. 1984 Nov;4(11):2877-90
references.pmid: 6150071
references.citation: J Physiol. 1993 Mar;462:47-58
references.pmid: 8392572
references.citation: Neuroscience. 1989;31(2):355-62
references.pmid: 2552348
references.citation: Biophys J. 1997 Mar;72(3):1458-71
references.pmid: 9138591
references.citation: Biophys J. 2000 May;78(5):2655-67
references.pmid: 10777761
references.citation: Neuron. 2002 Jan 31;33(3):439-52
references.pmid: 11832230
references.citation: Neuroscience. 2006 Jun 30;140(2):623-33
references.pmid: 16564639
references.citation: J Physiol. 1993 May;464:165-81
references.pmid: 8229797
references.citation: Neurosci Lett. 1989 Sep 25;104(1-2):53-7
references.pmid: 2812536
references.citation: J Neurosci. 1993 Mar;13(3):1157-66
references.pmid: 8441005
references.citation: Brain Res Brain Res Rev. 1997 Dec;25(3):312-34
references.pmid: 9495561
references.citation: J Physiol. 2001 Aug 15;535(Pt 1):17-31
references.pmid: 11507155
references.citation: J Neurosci. 2001 May 15;21(10):3443-56
references.pmid: 11331374
references.citation: J Neurosci. 2008 Apr 9;28(15):3877-86
references.pmid: 18400886
references.citation: J Biol Chem. 1985 Mar 25;260(6):3440-50
references.pmid: 3838314
references.citation: Neuroscience. 2002;114(2):475-92
references.pmid: 12204216
references.citation: Eur J Neurosci. 2001 Feb;13(4):757-62
references.pmid: 11207810
references.citation: J Neurosci. 2002 May 1;22(9):3404-13
references.pmid: 11978817
references.citation: J Physiol. 1993 Jul;466:727-47
references.pmid: 8410714
references.citation: Neuroscience. 1983 Oct;10(2):317-31
references.pmid: 6633864
references.citation: J Neurophysiol. 1999 Dec;82(6):2936-46
references.pmid: 10601430
references.citation: J Physiol. 1996 Nov 1;496 ( Pt 3):617-25
references.pmid: 8930830
references.citation: J Neurosci. 1995 Apr;15(4):2777-87
references.pmid: 7722628
references.citation: J Neurophysiol. 1992 Oct;68(4):1167-77
references.pmid: 1432076
references.citation: J Neurosci. 2007 Jan 17;27(3):645-56
references.pmid: 17234596
references.citation: J Neurophysiol. 1999 Mar;81(3):977-84
references.pmid: 10085326
references.citation: PLoS Genet. 2006 Aug;2(8):e128
references.pmid: 16895436
references.citation: J Neurosci. 2005 Jan 19;25(3):558-65
references.pmid: 15659591
references.citation: J Neurophysiol. 2006 Feb;95(2):932-47
references.pmid: 16207783
references.citation: Brain Res. 2004 Sep 3;1019(1-2):293-6
references.pmid: 15306267
references.citation: Behav Brain Res. 2002 Mar 10;130(1-2):149-69
references.pmid: 11864731
references.citation: Neurosci Res. 1993 Dec;18(3):209-21
references.pmid: 8127469
references.citation: J Physiol. 2008 Apr 15;586(8):2031
references.pmid: 18413335
references.citation: Neuroscience. 1999 Mar;89(3):813-25
references.pmid: 10199615
references.citation: Lancet Neurol. 2007 Oct;6(10):933-8
references.pmid: 17884683
references.citation: J Neurosci. 1995 Dec;15(12):7940-52
references.pmid: 8613732
references.citation: J Neurosci. 1987 Sep;7(9):2794-806
references.pmid: 3625274
references.citation: Brain Res. 1999 Oct 30;846(1):129-36
references.pmid: 10536220
references.citation: J Physiol. 1999 Oct 15;520 Pt 2:485-502
references.pmid: 10523417
references.citation: J Neurosci. 1989 Oct;9(10):3463-81
references.pmid: 2795134
references.citation: Biophys J. 1996 Feb;70(2):1069-81
references.pmid: 8789126
references.citation: Neuron. 1995 Sep;15(3):637-47
references.pmid: 7546743
references.citation: Neuroscience. 1983 Oct;10(2):301-15
references.pmid: 6633863
references.citation: J Physiol. 1994 Dec 1;481 ( Pt 2):251-71
references.pmid: 7738824
references.citation: J Comput Neurosci. 2003 Jul-Aug;15(1):53-69
references.pmid: 12843695
references.citation: J Comp Neurol. 1996 Jan 01;364(1):121-50
references.pmid: 8789281
references.citation: J Neurosci. 1992 Nov;12(11):4202-23
references.pmid: 1359030
references.citation: J Physiol. 1991 May;436:643-67
references.pmid: 2061849
references.citation: Br J Pharmacol. 1994 Nov;113(3):831-8
references.pmid: 7858874
references.citation: J Physiol. 2008 Apr 15;586(8):2061-75
references.pmid: 18276734
references.citation: Neuropharmacology. 1995 Nov;34(11):1423-42
references.pmid: 8606791
references.citation: Mol Endocrinol. 2001 Jul;15(7):1211-21
references.pmid: 11435619
references.citation: J Neurophysiol. 1995 Oct;74(4):1395-403
references.pmid: 8989380
references.citation: Brain Res. 1986 Apr 30;372(1):21-30
references.pmid: 3708356
references.citation: J Neurophysiol. 2004 Mar;91(3):1450-4
references.pmid: 14645383
references.citation: Nature. 2007 Jun 28;447(7148):1081-6
references.pmid: 17558391
references.citation: Brain Res Dev Brain Res. 1997 Oct 20;103(1):9-20
references.pmid: 9370056
references.citation: Neuron. 2002 Oct 10;36(2):285-98
references.pmid: 12383782
references.citation: Neuron. 2002 Oct 10;36(2):241-63
references.pmid: 12383780
references.citation: J Physiol. 1992 May;450:273-301
references.pmid: 1331424
references.citation: J Neurophysiol. 2000 May;83(5):3084-100
references.pmid: 10805703
references.citation: J Physiol. 1993 Sep;469:245-73
references.pmid: 8271200
references.citation: J Neurophysiol. 2004 Jan;91(1):324-35
references.pmid: 12917389
references.citation: Neuroscience. 1992;48(2):423-37
references.pmid: 1603327
references.citation: J Physiol. 2000 Jun 1;525 Pt 2:405-18
references.pmid: 10835043
references.citation: J Physiol. 2003 Jul 1;550(Pt 1):83-101
references.pmid: 12879862
references.citation: J Neurophysiol. 1997 Jan;77(1):145-52
references.pmid: 9120555