Quantitative analysis of mitochondrial Ca2+ uptake and release pathways in sympathetic neurons. Reconstruction of the recovery after depolarization-evoked [Ca2+]i elevations. J Gen Physiol 2000 Mar;115(3):371-88
Date
02/29/2000Pubmed ID
10694264Pubmed Central ID
PMC2217213DOI
10.1085/jgp.115.3.371Scopus ID
2-s2.0-0033818161 (requires institutional sign-in at Scopus site) 63 CitationsAbstract
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 approximately 300 nM increase intramitochondrial total Ca2+ concentration, but the steady [Ca2+]i elevations evoked by such stimuli are not influenced by FCCP.
Author List
Colegrove SL, Albrecht MA, Friel DDAuthor
Meredith A. Albrecht MD, PhD Associate Professor in the Anesthesiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Action PotentialsAnimals
Calcium
Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone
Cell Membrane
Clonazepam
Electrophysiology
Male
Membrane Potentials
Mitochondria
Neurons
Potassium
Rana catesbeiana
Sodium-Calcium Exchanger
Stimulation, Chemical
Sympathetic Nervous System
Thiazepines
Uncoupling Agents
