Endogenous calcium buffering capacity of substantia nigral dopamine neurons

Robert Foehring, X. F. Zhang, J. C.F. Lee, J. C. Callaway

Research output: Contribution to journalArticle

60 Citations (Scopus)

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 ([Ca2+]i) elicit several events in DA cells, including spike afterhyperpolarizations (AHPs) and subthreshold oscillations underlying autonomous firing. Continuous Ca2+ 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 [Ca2+]i in DA cells, we characterized their intrinsic Ca2+-buffering capacity (KS) in brain slices. We introduced a fluorescent Ca2+-sensitive exogenous buffer (200 μM 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 Ca2+ transient from the proximal dendrite. DA neurons filled exponentially with a τ of about 5-6 min. [Ca2+] i was assumed to equilibrate between the endogenous Ca2+ buffer and the exogenous Ca2+ indicator buffer. Intrinsic buffering was estimated by extrapolating from the linear relationships between the amplitude or time constant of the Ca2+ transients versus [fura-2]. Extrapolated Ca2+-transients in the absence of fura-2 had mean peak amplitudes of 293.7 ± 65.3 nM and τ = 124 ± 13 ms (postnatal day 13 [P13] to P17 animals). Intrinsic buffering increased with age in DA neurons. For cells from animals P13-P17, KS 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 Ca2+ 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 Ca2+-dependent pathology.

Original languageEnglish (US)
Pages (from-to)2326-2333
Number of pages8
JournalJournal of neurophysiology
Volume102
Issue number4
DOIs
StatePublished - Oct 1 2009

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Dopaminergic Neurons
Substantia Nigra
Calcium
Dopamine
Buffers
Fura-2
Parkinson Disease
Periodicity
Dendrites
Action Potentials
Cause of Death
Ions
Pathology
Brain

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Physiology

Cite this

Endogenous calcium buffering capacity of substantia nigral dopamine neurons. / Foehring, Robert; Zhang, X. F.; Lee, J. C.F.; Callaway, J. C.

In: Journal of neurophysiology, Vol. 102, No. 4, 01.10.2009, p. 2326-2333.

Research output: Contribution to journalArticle

Foehring, Robert ; Zhang, X. F. ; Lee, J. C.F. ; Callaway, J. C. / Endogenous calcium buffering capacity of substantia nigral dopamine neurons. In: Journal of neurophysiology. 2009 ; Vol. 102, No. 4. pp. 2326-2333.
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