Endogenous calcium buffering capacity of substantia nigral dopamine neurons.
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.
Foehring
R C
RC
Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, University of Tennessee, Memphis, Tennessee 38163, USA. rfoehrin@utmem.edu
Zhang
X F
XF
Lee
J C F
JC
Callaway
J C
JC
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*
D002118:Calcium; D016257:Fura-2; D004298:Dopamine
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