|
|
|
|
|
|
|
||
Original Article |
ddf2{at}po.cwru.edu
We studied how mitochondrial Ca2+ transport influences [Ca2+]i dynamics in sympathetic neurons. Cells were treated with thapsigargin to inhibit Ca2+ accumulation by SERCA pumps and depolarized to elevate [Ca2+]i; the recovery that followed repolarization was then examined. The total Ca2+ flux responsible for the [Ca2+]i recovery was separated into mitochondrial and nonmitochondrial components based on sensitivity to the proton ionophore FCCP, a selective inhibitor of mitochondrial Ca2+ transport in these cells. The nonmitochondrial flux, representing net Ca2+ extrusion across the plasma membrane, has a simple dependence on [Ca2+]i, while the net mitochondrial flux (Jmito) is biphasic, indicative of Ca2+ accumulation during the initial phase of recovery when [Ca2+]i is high, and net Ca2+ release during later phases of recovery. During each phase, mitochondrial Ca2+ transport has distinct effects on recovery kinetics. Jmito was separated into components representing mitochondrial Ca2+ uptake and release based on sensitivity to the specific mitochondrial Na+/Ca2+ exchange inhibitor, CGP 37157 (CGP). The CGP-resistant (uptake) component of Jmito increases steeply with [Ca2+]i, as expected for transport by the mitochondrial uniporter. The CGP-sensitive (release) component is inhibited by lowering the intracellular Na+ concentration and depends on both intra- and extramitochondrial Ca2+ concentration, as expected for the Na+/Ca2+ exchanger. Above
400 nM [Ca2+]i, net mitochondrial Ca2+ transport is dominated by uptake and is largely insensitive to CGP. When [Ca2+]i is 200–300 nM, the net mitochondrial flux is small but represents the sum of much larger uptake and release fluxes that largely cancel. Thus, mitochondrial Ca2+ transport occurs in situ at much lower concentrations than previously thought, and may provide a mechanism for quantitative control of ATP production after brief or low frequency stimuli that raise [Ca2+]i to levels below 500 nM.
Key Words: mitochondria • calcium • calcium signaling • neurons • CGP 37157
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Facebook 
Reddit 
Technorati 
Twitter What's this?
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]
|
|
|
|
|
|
E. F. Barrett Contrasting Contributions of Endoplasmic Reticulum and Mitochondria to Ca2+ Handling in Neurons J. Gen. Physiol., July 1, 2001; 118(1): 79 - 82. [Full Text] [PDF]
|
|
|
|
|
|
J. Hongpaisan, N. B. Pivovarova, S. L. Colegrove, R. D. Leapman, D. D. Friel, and S. B. Andrews Multiple Modes of Calcium-Induced Calcium Release in Sympathetic Neurons II: A [Ca2+]i- and Location-Dependent Transition from Endoplasmic Reticulum Ca Accumulation to Net Ca Release J. Gen. Physiol., July 1, 2001; 118(1): 101 - 112. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Akita and K. Kuba Functional Triads Consisting of Ryanodine Receptors, Ca2+ Channels, and Ca2+-Activated K+ Channels in Bullfrog Sympathetic Neurons: Plastic Modulation of Action Potential J. Gen. Physiol., November 1, 2000; 116(5): 697 - 720. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. V. Straub, D. R. Giovannucci, and D. I. Yule Calcium Wave Propagation in Pancreatic Acinar Cells: Functional Interaction of Inositol 1,4,5-Trisphosphate Receptors, Ryanodine Receptors, and Mitochondria J. Gen. Physiol., October 1, 2000; 116(4): 547 - 560. [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]
|
|
|
|
