Mitochondrial regulation of calcium in the avian cochlear nucleus.
The role of mitochondria and the endoplasmic reticulum in buffering [Ca2+]i in response to imposed calcium loads in neurons of the chick cochlear nucleus, nucleus magnocellularis (NM), was examined. Intracellular calcium concentrations were measured using fluorometric videomicroscopy. After depolarization with 125 mM KCl, NM neurons demonstrate an increase in [Ca2+]i that returns to near-basal levels within 6 min. Addition of the protonophore carbonylcyanide m-chlorophenylhydrazone (CCCP) dissipated the mitochondrial membrane potential, as evidenced by increased fluorescence when cells were loaded with rhodamine-123. Two micromolar CCCP had minimal effect on baseline [Ca2+]i. However, 2 or 10 microM CCCP interfered with the ability of NM cells to buffer [Ca2+]i in response to KCl depolarization without significantly affecting peak [Ca2+]i. Oligomycin also interfered with postdepolarization regulation of [Ca2+]i, but blocked late (7-8 min postdepolarization) increases in [Ca2+]i caused by CCCP. Thapsigargin had no effect on baseline, peak, or postdepolarization [Ca2+]i in NM cells. These results suggest that normal mitochondrial membrane potential and ATP synthesis play an important role in buffering [Ca2+]i in response to imposed calcium loads in NM neurons. Furthermore, the endoplasmic reticulum does not appear to play a significant role in either of these processes. Thus increases in mitochondrial number and function noted in NM cells after deafferentation may represent an adaptive response to an increased cytosolic calcium load.
Mostafapour
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SP
Virginia Merrill Bloedel Hearing Research Center, Department of Otolaryngology-Head and Neck Surgery, University of Washington School of Medicine, Seattle, Washington 98195, USA.
Lachica
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EA
Rubel
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EW
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002642:Chick Embryo; D017626:Cochlear Nucleus / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology*; D009840:Oligomycins / Q000494:pharmacology
D004791:Enzyme Inhibitors; D009840:Oligomycins; D002118:Calcium