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| Status |
Public on Jul 31, 2022 |
| Title |
Ca2+ channels couple spiking to mitochondrial metabolism in substantia nigra dopaminergic neurons |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
How do neurons match generation of adenosine triphosphate (ATP) by mitochondria to the bioenergetic demands of regenerative activity? Although the subject of speculation, this coupling is still poorly understood, particularly in neurons that are tonically active. To help fill this gap, pacemaking substantia nigra dopaminergic neurons were studied using a combination of optical, electrophysiological and molecular approaches. In these neurons, spike-activated calcium (Ca2+) entry through Cav1 channels triggered Ca2+ release from the endoplasmic reticulum, which stimulated mitochondrial OXPHOS through two complementary Ca2+-dependent mechanisms: one mediated by the mitochondrial uniporter and another by the malate-aspartate shuttle. Disrupting either mechanism impaired the ability of dopaminergic neurons to sustain spike activity. While this feedforward control helps dopaminergic neurons meet the bioenergetic demands associated with sustained spiking, it also is responsible for their elevated oxidant stress and possibly to their decline with aging and disease.
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| Overall design |
Comparative gene expression profiling analysis of RNA-seq data of MCU-KO and wildtype substantia nigra dopaminergic neurons selectively pulled-down with the RiboTag approach
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| Contributor(s) |
Zampese E, Wokosin DL, Gonzalez Rodriguez P, Guzman JN, Tkatch T, Kondapalli J, Surmeier WC, D'Alessandro KB, De Stefani D, Rizzuto R, Iino M, Molkentin JD, Chandel NS, Schumacker PT, Surmeier DJ |
| Citation(s) |
36179023 |
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| Submission date |
Jun 17, 2022 |
| Last update date |
Oct 31, 2022 |
| Contact name |
Enrico Zampese |
| E-mail(s) |
enrico.zampese@gmail.com, enrico.zampese@northwestern.edu
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| Organization name |
Northwestern University
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| Department |
Neuroscience
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| Lab |
Surmeier Lab
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| Street address |
303 E Superior st
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| City |
Chicago |
| State/province |
IL |
| ZIP/Postal code |
60611 |
| Country |
USA |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (16)
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| Relations |
| BioProject |
PRJNA850392 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE206366_RAW.tar |
1.6 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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