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RESEARCH-ARTICLE

Endogenous Calcium Buffering Capacity of Substantia Nigral Dopamine Neurons

Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, University of Tennessee, Memphis, Tennessee

Submitted 14 January 2009; accepted in final form 11 August 2009

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 Ca²⁺-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 (K_S) 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 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 = 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 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.