TY - JOUR
T1 -
Extracellular calcium depletion transiently elevates oxygen consumption in neurosecretory PC12 cells through activation of mitochondrial Na
+
/Ca
2+
exchange
AU - Zhdanov, Alexander V.
AU - Ward, Manus
AU - Taylor, Cormac T.
AU - Souslova, Ekaterina A.
AU - Chudakov, Dmitri M.
AU - Prehn, Jochen H.M.
AU - Papkovsky, Dmitri B.
PY - 2010/9/1
Y1 - 2010/9/1
N2 -
Fluctuating extracellular Ca
2+
regulates many aspects of neuronal (patho)physiology including cell metabolism and respiration. Using fluorescence-based intracellular oxygen sensing technique, we demonstrate that depletion of extracellular Ca
2+
from 1.8 to ≤0.6mM by chelation with EGTA induces a marked spike in O
2
consumption in differentiated PC12 cells. This respiratory response is associated with the reduction in cytosolic and mitochondrial Ca
2+
, minor depolarization on the mitochondrial membrane, moderate depolarization of plasma membrane, and no changes in NAD(P)H and ATP. The response is linked to the influx of extracellular Na
+
and the subsequent activation of mitochondrial Na
+
/Ca
2+
and Na
+
/H
+
exchange. The mitochondrial Na
+
/Ca
2+
exchanger (
m
NCX) activated by Na
+
influx reduces Ca
2+
and increases Na
+
levels in the mitochondrial matrix. The excess of Na
+
activates the mitochondrial Na
+
/H
+
exchanger (NHE) increasing the outward pumping of protons, electron transport and O
2
consumption. Reduction in extracellular Na
+
and inhibition of Na
+
influx through the receptor operated calcium channels and plasmalemmal NHE reduce the respiratory response. Inhibition of the
m
NCX, L-type voltage gated Ca
2+
channels or the release of Ca
2+
from the endoplasmic reticulum also reduces the respiratory spike, indicating that unimpaired intercompartmental Ca
2+
exchange is critical for response development.
AB -
Fluctuating extracellular Ca
2+
regulates many aspects of neuronal (patho)physiology including cell metabolism and respiration. Using fluorescence-based intracellular oxygen sensing technique, we demonstrate that depletion of extracellular Ca
2+
from 1.8 to ≤0.6mM by chelation with EGTA induces a marked spike in O
2
consumption in differentiated PC12 cells. This respiratory response is associated with the reduction in cytosolic and mitochondrial Ca
2+
, minor depolarization on the mitochondrial membrane, moderate depolarization of plasma membrane, and no changes in NAD(P)H and ATP. The response is linked to the influx of extracellular Na
+
and the subsequent activation of mitochondrial Na
+
/Ca
2+
and Na
+
/H
+
exchange. The mitochondrial Na
+
/Ca
2+
exchanger (
m
NCX) activated by Na
+
influx reduces Ca
2+
and increases Na
+
levels in the mitochondrial matrix. The excess of Na
+
activates the mitochondrial Na
+
/H
+
exchanger (NHE) increasing the outward pumping of protons, electron transport and O
2
consumption. Reduction in extracellular Na
+
and inhibition of Na
+
influx through the receptor operated calcium channels and plasmalemmal NHE reduce the respiratory response. Inhibition of the
m
NCX, L-type voltage gated Ca
2+
channels or the release of Ca
2+
from the endoplasmic reticulum also reduces the respiratory spike, indicating that unimpaired intercompartmental Ca
2+
exchange is critical for response development.
KW - Cell Metabolism
KW - Extracellular calcium
KW - Intracellular calcium
KW - Mitochondria
KW - Phosphorescent Oxygen-Sensitive Probe
KW - Respiration
UR - http://www.scopus.com/inward/record.url?scp=77954762248&partnerID=8YFLogxK
U2 - 10.1016/j.bbabio.2010.06.006
DO - 10.1016/j.bbabio.2010.06.006
M3 - Article
C2 - 20550942
AN - SCOPUS:77954762248
SN - 0005-2728
VL - 1797
SP - 1627
EP - 1637
JO - Biochimica et Biophysica Acta - Bioenergetics
JF - Biochimica et Biophysica Acta - Bioenergetics
IS - 9
ER -