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Original Article

Reconstruction of the Recovery after Depolarization-Evoked [Ca²⁺]_i Elevations

Stephen L. Colegrove^a, Meredith A. Albrecht^a, and David D. Friel^a

^a Department of Neuroscience, Case Western Reserve University, Cleveland, Ohio
Department of Neuroscience, Case Western Reserve University, 10900 Euclid Ave. Cleveland, OH 44106.(216) 368-4650

ddf2{at}po.cwru.edu

Rate equations for mitochondrial Ca²⁺ uptake and release and plasma membrane Ca²⁺ transport were determined from the measured fluxes in the preceding study and incorporated into a model of Ca²⁺ dynamics. It was asked if the measured fluxes are sufficient to account for the [Ca²⁺]_i recovery kinetics after depolarization-evoked [Ca²⁺]_i elevations. Ca²⁺ transport across the plasma membrane was described by a parallel extrusion/leak system, while the rates of mitochondrial Ca²⁺ uptake and release were represented using equations like those describing Ca²⁺ transport by isolated mitochondria. Taken together, these rate descriptions account very well for the time course of recovery after [Ca²⁺]_i elevations evoked by weak and strong depolarization and their differential sensitivity to FCCP, CGP 37157, and [Na⁺]_i. The model also leads to three general conclusions about mitochondrial Ca²⁺ transport in intact cells: (1) mitochondria are expected to accumulate Ca²⁺ even in response to stimuli that raise [Ca²⁺]_i only slightly above resting levels; (2) there are two qualitatively different stimulus regimes that parallel the buffering and non-buffering modes of Ca²⁺ transport by isolated mitochondria that have been described previously; (3) the impact of mitochondrial Ca²⁺ transport on intracellular calcium dynamics is strongly influenced by nonmitochondrial Ca²⁺ transport; in particular, the magnitude of the prolonged [Ca²⁺]_i elevation that occurs during the plateau phase of recovery is related to the Ca²⁺ set-point described in studies of isolated mitochondria, but is a property of mitochondrial Ca²⁺ transport in a cellular context. Finally, the model resolves the paradoxical finding that stimulus-induced [Ca²⁺]_i elevations as small as 300 nM increase intramitochondrial total Ca²⁺ concentration, but the steady [Ca²⁺]_i elevations evoked by such stimuli are not influenced by FCCP.

Key Words: mitochondria • calcium • neurons • Ca²⁺ uniporter • mitochondrial Na⁺/Ca²⁺ exchanger

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This article has been cited by other articles:

				M. A. Albrecht, S. L. Colegrove, J. Hongpaisan, N. B. Pivovarova, S. B. Andrews, and D. D. Friel Multiple Modes of Calcium-Induced Calcium Release in Sympathetic Neurons I: Attenuation of Endoplasmic Reticulum Ca2+ Accumulation at Low [Ca2+]i during Weak Depolarization J. Gen. Physiol., July 1, 2001; 118(1): 83 - 100. [Abstract] [Full Text] [PDF]

				L. K. Kaczmarek Mitochondrial Memory Banks: Calcium Stores Keep a Record of Neuronal Stimulation J. Gen. Physiol., March 1, 2000; 115(3): 347 - 350. [Full Text] [PDF]

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