Mitochondrial transport in processes of cortical neurons is independent of intracellular calcium.
Mitochondria show extensive movement along neuronal processes, but the mechanisms and function of this movement are not clearly understood. We have used high-resolution confocal microscopy to simultaneously monitor movement of mitochondria and changes in intracellular [Ca(2+)] ([Ca(2+)](i)) in rat cortical neurons. A significant percentage (27%) of the total mitochondria in cortical neuronal processes showed movement over distances of >2 microM. The average velocity was 0.52 microm/s. The velocity, direction, and pattern of mitochondrial movement were not affected by transient increases in [Ca(2+)](i) associated with spontaneous firing of action potentials. Stimulation of Ca(2+) transients with forskolin (10 microM) or bicuculline (10 microM), or sustained elevations of [Ca(2+)](i) evoked by glutamate (10 microM) also had no effect on mitochondrial transit. Neither removal of extracellular Ca(2+), depletion of intracellular Ca(2+) stores with thapsigargin, or inhibition of synaptic activity with TTX (1 microM) or a cocktail of CNQX (10 microM) and MK801 (10 microM) affected mitochondrial movement. These results indicate that movement of mitochondria along processes is a fundamental activity in neurons that occurs independently of physiological changes in [Ca(2+)](i) associated with action potential firing, synaptic activity, or release of Ca(2+) from intracellular stores.
Beltran-Parrazal
Luis
L
Department of Neurology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, USA.
López-Valdés
Héctor E
HE
Brennan
K C
KC
Díaz-Muñoz
Mauricio
M
de Vellis
Jean
J
Charles
Andrew C
AC
D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D001692:Biological Transport / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D005576:Colforsin / Q000378:metabolism; D005260:Female; D018756:GABA Antagonists / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
D000447:Aldehydes; D018756:GABA Antagonists; C111472:mitotracker green FM; D005576:Colforsin; D018698:Glutamic Acid; D002118:Calcium; D001640:Bicuculline