Dynamic changes in cytosolic ATP levels in cultured glutamatergic neurons during NMDA-induced synaptic activity supported by glucose or lactate

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Dynamic changes in cytosolic ATP levels in cultured glutamatergic neurons during NMDA-induced synaptic activity supported by glucose or lactate. / Lange, Sofie Cecilie; Winkler, Ulrike; Andresen, Lars; Byhrø, Mathilde; Waagepetersen, Helle S.; Hirrlinger, Johannes; Bak, Lasse Kristoffer.

In: Neurochemical Research, Vol. 40, No. 12, 12.2015, p. 2517-2526.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Lange, SC, Winkler, U, Andresen, L, Byhrø, M, Waagepetersen, HS, Hirrlinger, J & Bak, LK 2015, 'Dynamic changes in cytosolic ATP levels in cultured glutamatergic neurons during NMDA-induced synaptic activity supported by glucose or lactate', Neurochemical Research, vol. 40, no. 12, pp. 2517-2526. https://doi.org/10.1007/s11064-015-1651-9

APA

Lange, S. C., Winkler, U., Andresen, L., Byhrø, M., Waagepetersen, H. S., Hirrlinger, J., & Bak, L. K. (2015). Dynamic changes in cytosolic ATP levels in cultured glutamatergic neurons during NMDA-induced synaptic activity supported by glucose or lactate. Neurochemical Research, 40(12), 2517-2526. https://doi.org/10.1007/s11064-015-1651-9

Vancouver

Lange SC, Winkler U, Andresen L, Byhrø M, Waagepetersen HS, Hirrlinger J et al. Dynamic changes in cytosolic ATP levels in cultured glutamatergic neurons during NMDA-induced synaptic activity supported by glucose or lactate. Neurochemical Research. 2015 Dec;40(12):2517-2526. https://doi.org/10.1007/s11064-015-1651-9

Author

Lange, Sofie Cecilie ; Winkler, Ulrike ; Andresen, Lars ; Byhrø, Mathilde ; Waagepetersen, Helle S. ; Hirrlinger, Johannes ; Bak, Lasse Kristoffer. / Dynamic changes in cytosolic ATP levels in cultured glutamatergic neurons during NMDA-induced synaptic activity supported by glucose or lactate. In: Neurochemical Research. 2015 ; Vol. 40, No. 12. pp. 2517-2526.

Bibtex

@article{17eaacc493c042c1a4391b9b47fa76c0,
title = "Dynamic changes in cytosolic ATP levels in cultured glutamatergic neurons during NMDA-induced synaptic activity supported by glucose or lactate",
abstract = "We have previously shown that synaptic transmission fails in cultured neurons in the presence of lactate as the sole substrate. Thus, to test the hypothesis that the failure of synaptic transmission is a consequence of insufficient energy supply, ATP levels were monitored employing the ATP biosensor Ateam1.03YEMK. While inducing synaptic activity by subjecting cultured neurons to two 30 s pulses of NMDA (30 µM) with a 4 min interval, changes in relative ATP levels were measured in the presence of lactate (1 mM), glucose (2.5 mM) or the combination of the two. ATP levels reversibly declined following NMDA-induced neurotransmission activity, as indicated by a reversible 10-20 % decrease in the response of the biosensor. The responses were absent when the NMDA receptor antagonist memantine was present. In the presence of lactate alone, the ATP response dropped significantly more than in the presence of glucose following the 2nd pulse of NMDA (approx. 10 vs. 20 %). Further, cytosolic Ca(2+) homeostasis during NMDA-induced synaptic transmission is partially inhibited by verapamil indicating that voltage-gated Ca(2+) channels are activated. Lastly, we showed that cytosolic Ca(2+) homeostasis is supported equally well by both glucose and lactate, and that a pulse of NMDA causes accumulation of Ca(2+) in the mitochondrial matrix. In summary, we have shown that ATP homeostasis during neurotransmission activity in cultured neurons is supported by both glucose and lactate. However, ATP homeostasis seems to be negatively affected by the presence of lactate alone, suggesting that glucose is needed to support neuronal energy metabolism during activation.",
keywords = "Faculty of Health and Medical Sciences, Neuron, ATP, Glucose, Lactate dehydrogenase (LDH)",
author = "Lange, {Sofie Cecilie} and Ulrike Winkler and Lars Andresen and Mathilde Byhr{\o} and Waagepetersen, {Helle S.} and Johannes Hirrlinger and Bak, {Lasse Kristoffer}",
year = "2015",
month = dec,
doi = "10.1007/s11064-015-1651-9",
language = "English",
volume = "40",
pages = "2517--2526",
journal = "Neurochemical Research",
issn = "0364-3190",
publisher = "Springer",
number = "12",

}

RIS

TY - JOUR

T1 - Dynamic changes in cytosolic ATP levels in cultured glutamatergic neurons during NMDA-induced synaptic activity supported by glucose or lactate

AU - Lange, Sofie Cecilie

AU - Winkler, Ulrike

AU - Andresen, Lars

AU - Byhrø, Mathilde

AU - Waagepetersen, Helle S.

AU - Hirrlinger, Johannes

AU - Bak, Lasse Kristoffer

PY - 2015/12

Y1 - 2015/12

N2 - We have previously shown that synaptic transmission fails in cultured neurons in the presence of lactate as the sole substrate. Thus, to test the hypothesis that the failure of synaptic transmission is a consequence of insufficient energy supply, ATP levels were monitored employing the ATP biosensor Ateam1.03YEMK. While inducing synaptic activity by subjecting cultured neurons to two 30 s pulses of NMDA (30 µM) with a 4 min interval, changes in relative ATP levels were measured in the presence of lactate (1 mM), glucose (2.5 mM) or the combination of the two. ATP levels reversibly declined following NMDA-induced neurotransmission activity, as indicated by a reversible 10-20 % decrease in the response of the biosensor. The responses were absent when the NMDA receptor antagonist memantine was present. In the presence of lactate alone, the ATP response dropped significantly more than in the presence of glucose following the 2nd pulse of NMDA (approx. 10 vs. 20 %). Further, cytosolic Ca(2+) homeostasis during NMDA-induced synaptic transmission is partially inhibited by verapamil indicating that voltage-gated Ca(2+) channels are activated. Lastly, we showed that cytosolic Ca(2+) homeostasis is supported equally well by both glucose and lactate, and that a pulse of NMDA causes accumulation of Ca(2+) in the mitochondrial matrix. In summary, we have shown that ATP homeostasis during neurotransmission activity in cultured neurons is supported by both glucose and lactate. However, ATP homeostasis seems to be negatively affected by the presence of lactate alone, suggesting that glucose is needed to support neuronal energy metabolism during activation.

AB - We have previously shown that synaptic transmission fails in cultured neurons in the presence of lactate as the sole substrate. Thus, to test the hypothesis that the failure of synaptic transmission is a consequence of insufficient energy supply, ATP levels were monitored employing the ATP biosensor Ateam1.03YEMK. While inducing synaptic activity by subjecting cultured neurons to two 30 s pulses of NMDA (30 µM) with a 4 min interval, changes in relative ATP levels were measured in the presence of lactate (1 mM), glucose (2.5 mM) or the combination of the two. ATP levels reversibly declined following NMDA-induced neurotransmission activity, as indicated by a reversible 10-20 % decrease in the response of the biosensor. The responses were absent when the NMDA receptor antagonist memantine was present. In the presence of lactate alone, the ATP response dropped significantly more than in the presence of glucose following the 2nd pulse of NMDA (approx. 10 vs. 20 %). Further, cytosolic Ca(2+) homeostasis during NMDA-induced synaptic transmission is partially inhibited by verapamil indicating that voltage-gated Ca(2+) channels are activated. Lastly, we showed that cytosolic Ca(2+) homeostasis is supported equally well by both glucose and lactate, and that a pulse of NMDA causes accumulation of Ca(2+) in the mitochondrial matrix. In summary, we have shown that ATP homeostasis during neurotransmission activity in cultured neurons is supported by both glucose and lactate. However, ATP homeostasis seems to be negatively affected by the presence of lactate alone, suggesting that glucose is needed to support neuronal energy metabolism during activation.

KW - Faculty of Health and Medical Sciences

KW - Neuron

KW - ATP

KW - Glucose

KW - Lactate dehydrogenase (LDH)

U2 - 10.1007/s11064-015-1651-9

DO - 10.1007/s11064-015-1651-9

M3 - Journal article

C2 - 26184116

VL - 40

SP - 2517

EP - 2526

JO - Neurochemical Research

JF - Neurochemical Research

SN - 0364-3190

IS - 12

ER -

ID: 144000980