Endogenous XXXX buffering capacity of substantia nigral @entity935 neurons.

@entity935 @entity191 @entity593 @entity4148 @entity460 @entity141
@entity935 (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 @entity191 ( @entity191 ). Changes in intracellular @entity460 ion concentration ([ @entity141 ](i)) elicit several events in DA cells, including spike afterhyperpolarizations (AHPs) and subthreshold oscillations underlying autonomous firing. Continuous @entity141 load due to @entity141 -dependent rhythmicity has been proposed to cause the death of DA cells in @entity191 and normal aging. Because of the physiological and pathophysiological importance of [ @entity141 ](i) in DA cells, we characterized their intrinsic @entity141 -buffering capacity (K(S)) in brain slices. We introduced a fluorescent @entity141 -sensitive exogenous buffer (200 microM @entity593 ) and cells were tracked from break-in until steady state by stimulating with a single action potential (AP) every 30 s and measuring the @entity141 transient from the proximal dendrite. DA neurons filled exponentially with a tau of about 5-6 min. [ @entity141 ](i) was assumed to equilibrate between the endogenous @entity141 buffer and the exogenous @entity141 indicator buffer. Intrinsic buffering was estimated by extrapolating from the linear relationships between the amplitude or time constant of the @entity141 transients versus [ @entity593 ]. Extrapolated @entity141 -transients in the absence of @entity593 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 @entity141 signaling, e.g., to allow activation of sK channels, which shape @entity4148 and burst firing. Low intrinsic buffering may also make DA cells vulnerable to @entity141 -dependent pathology.
