Endogenous Calcium Buffering Capacity of Substantia Nigral Dopamine Neurons
2009
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 (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.
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