Endogenous Calcium Buffering Capacity of Substantia Nigral Dopamine Neurons

J Neurophysiol. 2009 Oct;102(4):2326-33. doi: 10.1152/jn.00038.2009. Epub 2009 Aug 12.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Action Potentials / physiology
  • Aging / physiology
  • Algorithms
  • Animals
  • Calcium / metabolism*
  • Dendrites / physiology
  • Dopamine / metabolism*
  • Fura-2
  • In Vitro Techniques
  • Kinetics
  • Linear Models
  • Membrane Potentials / physiology
  • Neurons / physiology*
  • Patch-Clamp Techniques
  • Rats
  • Rats, Sprague-Dawley
  • Substantia Nigra / physiology*

Substances

  • Calcium
  • Fura-2
  • Dopamine