The Na+/K+ pump dominates control of glycolysis in hippocampal dentate granule cells
Cellular ATP that is consumed to perform energetically expensive tasks must be replenished by new ATP through the activation of metabolism. Neuronal stimulation, an energetically demanding process, transiently activates aerobic glycolysis, but the precise mechanism underlying this glycolysis activat...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2022-10-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/81645 |
| _version_ | 1798030803408519168 |
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| author | Dylan J Meyer Carlos Manlio Díaz-García Nidhi Nathwani Mahia Rahman Gary Yellen |
| author_facet | Dylan J Meyer Carlos Manlio Díaz-García Nidhi Nathwani Mahia Rahman Gary Yellen |
| author_sort | Dylan J Meyer |
| collection | DOAJ |
| description | Cellular ATP that is consumed to perform energetically expensive tasks must be replenished by new ATP through the activation of metabolism. Neuronal stimulation, an energetically demanding process, transiently activates aerobic glycolysis, but the precise mechanism underlying this glycolysis activation has not been determined. We previously showed that neuronal glycolysis is correlated with Ca2+ influx, but is not activated by feedforward Ca2+ signaling (Díaz-García et al., 2021a). Since ATP-powered Na+ and Ca2+ pumping activities are increased following stimulation to restore ion gradients and are estimated to consume most neuronal ATP, we aimed to determine if they are coupled to neuronal glycolysis activation. By using two-photon imaging of fluorescent biosensors and dyes in dentate granule cell somas of acute mouse hippocampal slices, we observed that production of cytoplasmic NADH, a byproduct of glycolysis, is strongly coupled to changes in intracellular Na+, while intracellular Ca2+ could only increase NADH production if both forward Na+/Ca2+ exchange and Na+/K+ pump activity were intact. Additionally, antidromic stimulation-induced intracellular [Na+] increases were reduced >50% by blocking Ca2+ entry. These results indicate that neuronal glycolysis activation is predominantly a response to an increase in activity of the Na+/K+ pump, which is strongly potentiated by Na+ influx through the Na+/Ca2+ exchanger during extrusion of Ca2+ following stimulation. |
| first_indexed | 2024-04-11T19:46:10Z |
| format | Article |
| id | doaj.art-97a6265081a44ccd83fd78b6d945ec2f |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T19:46:10Z |
| publishDate | 2022-10-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-97a6265081a44ccd83fd78b6d945ec2f2022-12-22T04:06:28ZengeLife Sciences Publications LtdeLife2050-084X2022-10-011110.7554/eLife.81645The Na+/K+ pump dominates control of glycolysis in hippocampal dentate granule cellsDylan J Meyer0https://orcid.org/0000-0001-8453-3813Carlos Manlio Díaz-García1https://orcid.org/0000-0002-4352-2496Nidhi Nathwani2Mahia Rahman3Gary Yellen4https://orcid.org/0000-0003-4228-7866Department of Neurobiology, Harvard Medical School, Boston, United StatesDepartment of Neurobiology, Harvard Medical School, Boston, United StatesDepartment of Neurobiology, Harvard Medical School, Boston, United StatesDepartment of Neurobiology, Harvard Medical School, Boston, United StatesDepartment of Neurobiology, Harvard Medical School, Boston, United StatesCellular ATP that is consumed to perform energetically expensive tasks must be replenished by new ATP through the activation of metabolism. Neuronal stimulation, an energetically demanding process, transiently activates aerobic glycolysis, but the precise mechanism underlying this glycolysis activation has not been determined. We previously showed that neuronal glycolysis is correlated with Ca2+ influx, but is not activated by feedforward Ca2+ signaling (Díaz-García et al., 2021a). Since ATP-powered Na+ and Ca2+ pumping activities are increased following stimulation to restore ion gradients and are estimated to consume most neuronal ATP, we aimed to determine if they are coupled to neuronal glycolysis activation. By using two-photon imaging of fluorescent biosensors and dyes in dentate granule cell somas of acute mouse hippocampal slices, we observed that production of cytoplasmic NADH, a byproduct of glycolysis, is strongly coupled to changes in intracellular Na+, while intracellular Ca2+ could only increase NADH production if both forward Na+/Ca2+ exchange and Na+/K+ pump activity were intact. Additionally, antidromic stimulation-induced intracellular [Na+] increases were reduced >50% by blocking Ca2+ entry. These results indicate that neuronal glycolysis activation is predominantly a response to an increase in activity of the Na+/K+ pump, which is strongly potentiated by Na+ influx through the Na+/Ca2+ exchanger during extrusion of Ca2+ following stimulation.https://elifesciences.org/articles/81645glycolysisNa-Ca exchangeNa-K pumpcytosolic NADHneurons |
| spellingShingle | Dylan J Meyer Carlos Manlio Díaz-García Nidhi Nathwani Mahia Rahman Gary Yellen The Na+/K+ pump dominates control of glycolysis in hippocampal dentate granule cells eLife glycolysis Na-Ca exchange Na-K pump cytosolic NADH neurons |
| title | The Na+/K+ pump dominates control of glycolysis in hippocampal dentate granule cells |
| title_full | The Na+/K+ pump dominates control of glycolysis in hippocampal dentate granule cells |
| title_fullStr | The Na+/K+ pump dominates control of glycolysis in hippocampal dentate granule cells |
| title_full_unstemmed | The Na+/K+ pump dominates control of glycolysis in hippocampal dentate granule cells |
| title_short | The Na+/K+ pump dominates control of glycolysis in hippocampal dentate granule cells |
| title_sort | na k pump dominates control of glycolysis in hippocampal dentate granule cells |
| topic | glycolysis Na-Ca exchange Na-K pump cytosolic NADH neurons |
| url | https://elifesciences.org/articles/81645 |
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