. 2022 Sep 30;8(39):eabp8701.

doi: 10.1126/sciadv.abp8701. Epub 2022 Sep 30.

Ca²⁺ channels couple spiking to mitochondrial metabolism in substantia nigra dopaminergic neurons

Enrico Zampese^{1

2}, David L Wokosin^{1

2}, Patricia Gonzalez-Rodriguez^{1

2}, Jaime N Guzman^{1

2}, Tatiana Tkatch^{1

2}, Jyothisri Kondapalli^{1

2}, William C Surmeier^{1

2}, Karis B D'Alessandro³, Diego De Stefani⁴, Rosario Rizzuto⁴, Masamitsu Iino⁵, Jeffery D Molkentin⁶, Navdeep S Chandel³, Paul T Schumacker⁷, D James Surmeier^{1

2}

Affiliations

¹ Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
² Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA.
³ Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
⁴ Department of Biomedical Sciences, University of Padova, Padova 35131, Italy.
⁵ Department of Physiology, Nihon University School of Medicine, 30-1, Oyaguchi Kami-cho, Itabashi-ku, Tokyo 173-8610, Japan.
⁶ Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH 45229, USA.
⁷ Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.

PMID: 36179023
PMCID: PMC9524841
DOI: 10.1126/sciadv.abp8701

Ca²⁺ channels couple spiking to mitochondrial metabolism in substantia nigra dopaminergic neurons

Enrico Zampese et al. Sci Adv. 2022.

. 2022 Sep 30;8(39):eabp8701.

doi: 10.1126/sciadv.abp8701. Epub 2022 Sep 30.

Authors

Affiliations

¹ Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
² Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA.
³ Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
⁴ Department of Biomedical Sciences, University of Padova, Padova 35131, Italy.
⁵ Department of Physiology, Nihon University School of Medicine, 30-1, Oyaguchi Kami-cho, Itabashi-ku, Tokyo 173-8610, Japan.
⁶ Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH 45229, USA.
⁷ Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.

PMID: 36179023
PMCID: PMC9524841
DOI: 10.1126/sciadv.abp8701

Abstract

How do neurons match generation of adenosine triphosphate 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 Ca_v1 channels triggered Ca²⁺ release from the endoplasmic reticulum, which stimulated mitochondrial oxidative phosphorylation 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 is also responsible for their elevated oxidant stress and possibly to their decline with aging and disease.

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Figures

**Fig. 1.. Ca²⁺ entry through Ca_v1 Ca²⁺ channels triggered ER Ca²⁺ release.**
(A) Representative reconstruction of a Fura-2–filled SNc dopaminergic neuron (scale bar, 20 μm). (B) Representative whole-cell current clamp recordings (top) and 2PLSM traces of cytosolic Ca²⁺ oscillations (bottom) in SNc neurons loaded with Fura-2, before and after application of RYR antagonist DHBP. (C and D) Box plots summarizing the average amplitude of cytosolic Ca²⁺ oscillations and average Ca²⁺ concentration in dopaminergic neurons in control conditions and after DHBP bath application; DHBP significantly decreased the amplitude of cytosolic Ca²⁺ oscillations (n = 5, N = 5; P = 0.0312, one-tailed Wilcoxon matched-pairs signed rank test). (E) Cartoon representing the AAV delivery strategy to induce expression of G-CEPIA1er in midbrain dopaminergic neurons; modified from the Allen Mouse Brain Atlas, online version 1, 2008 (https://atlas.brain-map.org/). (F to H) Immunofluorescence images showing the expression of G-CEPIA1er in dopaminergic neurons stained for TH and the colocalization of G-CEPIA1er with the ER marker calreticulin (CRT); scale bars, 100 μm (F) and 10 μm (G and H). (I) Representative 2PLSM imaging time series showing the effect of application of Ca_v1 Ca²⁺ channel (Ca_v1)–positive allosteric modulator Bay K8644 (BAYK) on dendritic ER Ca²⁺ in SNc dopaminergic neurons expressing G-CEPIA1er. (J) Quantification of the effect of BAYK on dendritic ER Ca²⁺ measured with G-CEPIA1er (n = 8, N = 7; P = 0.0039, one-tailed Wilcoxon matched-pairs signed rank test). (K) Cartoon illustrating the effect of Ca²⁺ entry through Ca_v1 channels on RYR Ca²⁺ release and the targets of BAYK and DHBP. Box plots indicate first and third quartiles, thick center lines represent medians, and whiskers indicate the range. a.u., arbitrary units. *P < 0.05.

**Fig. 2.. RYR and Ca_v1 channels determine elevated intra-mitochondrial Ca²⁺ in SNc dopaminergic neurons.**
(A) Cartoon representing the AAV delivery strategy to express mito-GCaMP6 in midbrain dopaminergic neurons; modified from the Allen Mouse Brain Atlas, online version 1, 2008 (https://atlas.brain-map.org/). (B to D) Immunofluorescence images showing the expression of mito-GCaMP6 in dopaminergic neurons stained for TH and the colocalization of mito-GCaMP6 with the mitochondrial marker COXIV; scale bars, 100 μm (B) and 10 μm (C and D). (E) Representative 2PLSM imaging time series showing the estimation of baseline mitochondrial Ca²⁺ levels in SNc (black) and VTA (gray) dopaminergic neurons expressing mito-GCaMP6. The Ca²⁺ ionophore ionomycin (iono) is used to allow the movement of Ca²⁺ through membranes according to its concentration gradient. (F) Mitochondrial Ca²⁺ levels in SNc and VTA dopaminergic neurons estimated with mito-GCaMP6 (n = 10, N = 10; n = 7, N = 7 for SNc and VTA, respectively; P = 0.0136, two-tailed Mann-Whitney test). (G) Dendritic and somatic mitochondrial Ca²⁺ levels in SNc dopaminergic neurons estimated with mito-GCaMP6 (n = 10, N = 9; P = 0.0273, two-tailed Wilcoxon matched-pairs signed rank test). (H) Cartoon illustrating the effect of Ca²⁺ entry through Ca_v1 channels and RYR Ca²⁺ release on mitochondrial Ca²⁺ loading and the targets of isradipine and DHBP. (I) Representative 2PLSM imaging time series showing the effect of application of DHBP on mitochondrial Ca²⁺ in SNc neurons. (J) Effect of DHBP (100 μM) on mitochondrial Ca²⁺ measured with mito-GCaMP6 (n = 6, N = 4; P = 0.0156, one-tailed Wilcoxon matched-pairs signed rank test). (K) Representative 2PLSM imaging time series showing the effect of application of Ca_v1-negative allosteric modulator isradipine (Isr) on mitochondrial Ca²⁺ in SNc neurons. (L) Effect of isradipine (0.5 to 1 μM) on mitochondrial Ca²⁺ measured with mito-GCaMP6 (n = 10, N = 9; P = 0.0010, one-tailed Wilcoxon matched-pairs signed rank test). Box plots indicate first and third quartiles, thick center lines represent medians, and whiskers indicate the range. *P < 0.05, **P < 0.01.

**Fig. 3.. Mitochondrial matrix Ca²⁺ tracks spike rate.**
(A) Left: Cartoon representing the strategy to monitor mitochondrial Ca²⁺ dynamics during changes in firing frequency via perforated-patch recording configuration. Right: Representative experiment illustrating the electrophysiological recording (gray, dotted line indicates −45 mV) and mito-GCaMP6 trace (green) during current injection. (B) Plot illustrating the distribution of normalized mito-GCaMP6 fluorescence over the normalized spike rate in SNc dopaminergic neurons (linear fit and 95% confidence interval, n = 4, N = 4). (C) 2PLSM image of an SNc dopaminergic neuron expressing mito-GCaMP6 and filled with Alexa Fluor 594 dye after inducing break-in at the end of a perforated-patch recording coupled with mito-GCaMP6 imaging in the somatic and dendritic regions, highlighted in the insets (scale bars: 50 μm, main image; 10 μm, insets). (D) Plot illustrating the distribution of normalized mito-GCaMP6 fluorescence over the normalized spike rate for dendritic (gray, empty symbols) and somatic (black, filled symbols) mitochondria, within the same SNc dopaminergic neurons (empty/filled symbols of the same shape indicate paired measurements from the same neuron; n = 5, N = 5; soma: linear fit and 95% confidence interval; dendritic measurements were better fitted by a third-order polynomial fit and 95% confidence interval). (E) Distribution of the normalized mito-GCaMP6 fluorescence in dendritic and somatic mitochondria at 50% of the baseline spike rate (n = 5, N = 5; P = 0.0050, two-tailed paired t test). Box plots indicate first and third quartiles, thick center lines represent medians, and whiskers indicate the range. **P < 0.01.

**Fig. 4.. The Ca_v1-RYR couple drives mitochondrial OXPHOS.**
(A and B) Immunofluorescence images showing the expression of PercevalHR in dopaminergic neurons stained for TH; scale bars, 100 μm (A) and 10 μm (B). (C) Schematic representing the contribution of glycolysis and mitochondrial OXPHOS to the production of ATP and maintenance of the ATP/ADP ratio, measured with PercevalHR; the actions of 2-DG and oligomycin are indicated. (D) Representative PercevalHR experiment estimating the contribution of mitochondria (inhibited by oligomycin) and glycolysis (inhibited by 2-DG) to the ATP/ADP ratio of the cell; the fluorescence measured for each of the two wavelengths (950 for ATP, 820 for ADP; gray traces) and the F950/F820 ratio calculated for each time point (black trace) are illustrated. (E) Cartoon illustrating the effect of Ca²⁺ entry through Ca_v1 channels and RYR Ca²⁺ release on mitochondrial ATP production and the action of isradipine and DHBP. (F) Representative 2PLSM ratio imaging time series showing the effect of application of Ca_v1 antagonist isradipine (Isr; 1 μM), followed by oligomycin (Oligo; 10 μM) and substitution of glucose with 2-DG on PercevalHR ratio in SNc dopaminergic neurons expressing PercevalHR. (G) Quantification of the effect of isradipine (1 μM) and DHBP (100 μM) on ATP/ADP ratio in SNc neurons expressing PercevalHR (isradipine, n = 11, N = 8; P = 0.0049, one-tailed Wilcoxon matched-pairs signed rank test; DHBP, n = 10, N = 6; P = 0.032, one-tailed Wilcoxon matched-pairs signed rank test). Box plots indicate first and third quartiles, thick center lines represent medians, and whiskers indicate the range. *P < 0.05, **P < 0.01.

**Fig. 5.. Feedforward stimulation of mitochondria by Ca²⁺ is required to sustain firing.**
(A) Representative perforated-patch and PercevalHR 2PLSM imaging experiment in SNc dopaminergic neurons modulating spike rate with current injections; spike rate, gray; ATP/ADP, black; current depolarizing steps (top), 50 pA. (B) Quantification of PercevalHR ratio upon changes in spike rate as in (A) for control (black) and isradipine-treated (0.5 μM, red) neurons; medians, range, and individual points are depicted (controls: n = 9, N = 9; isradipine: n = 6, N = 6). (C) Representative plots of instantaneous CV (continuous traces) and spike rate (dashed traces) for control (black) and isradipine-treated (red) cells during the depolarization steps [see (A)]. (D) Cumulative probability plots of cells undergoing failure to sustain firing at different time points for control (black) and isradipine-treated (red) SNc neurons during the current injection protocol in (A) (control: n = 9, N = 9; isradipine: n = 6, N = 6; P = 0.0028, Mantel-Cox test). (E) Representative recordings for control (black) and isradipine-treated (red) dopaminergic neurons during the depolarization steps. (F) Representative plots showing the correlation between spike rate (x axis), CV (y axis, logarithmic scale), and ATP/ADP ratio (colorimetric scale) for control and isradipine-treated cells; the colorimetric scale indicates the maximum (yellow), the minimum (dark purple), and the intermediate ratio values recorded within each experiment; see fig. S5 for details. (G) Representative recordings of isradipine-treated SNc neurons in standard glucose (3.5 mM) aCSF and 25 mM glucose aCSF. (H) Effect of glucose concentration on spike rate of SNc isradipine-treated neurons (n = 6, N = 5; P = 0.0156, one-tailed Wilcoxon matched-pairs signed rank test). (I) Effect of increasing glucose concentration on the CV of isradipine-treated neurons (n = 6, N = 5; P = 0.0156, one-tailed Wilcoxon matched-pairs signed rank test). Scale bars (E and G), 20 mV, 1 s. Box plots indicate first and third quartiles, thick center lines represent medians, and whiskers indicate the range. *P < 0.05.

**Fig. 6.. Loss of MCU disrupts mitochondrial Ca²⁺ uptake but results in a modest phenotype.**
(A) Quantification of the relative expression of *Mcu* mRNA in SNc dopaminergic neurons collected with the RiboTag strategy from wild-type and MCU-KO mice (N = 5 and 6 for wild type and MCU-KO, respectively; P = 0.0022, one-tailed Mann-Whitney test). (B) Cartoon illustrating the pathways leading to mitochondrial Ca²⁺ uptake tested in wild-type and MCU-KO neurons expressing mito-GCaMP6: Ca²⁺ entry through Ca_v1 triggers gates RYRs and release of Ca²⁺ at the “mitochondria-associated membrane” (mam); stimulation of mGluRs coupled to PLC generates IP₃, that gates IP₃R and induces release of Ca²⁺ at the mam; the MCU complex is gated by high Ca²⁺ microdomains and allows accumulation of Ca²⁺ into the mitochondrial matrix. (C) Representative 2PLSM mito-GCaMP6 traces of wild-type (gray) and MCU-KO (black) SNc dopaminergic neurons stimulated with the mGluR-I agonist DHPG (10 μM). (D) Quantification of mitochondrial baseline Ca²⁺ in wild-type and MCU-KO dopaminergic neurons expressing mito-GCaMP6 (n = 10, N = 9; n = 9, N = 8 for wild-type and MCU-KO, respectively; P = 0.0086, one-tailed Mann Whitney test). (E) Quantification of mitochondrial Ca²⁺ uptake upon DHPG stimulation in wild-type and MCU-KO SNc neurons expressing mito-GCaMP6; the area under the curve (AUC) is calculated over 90 s from the start of the peak (n = 10, N = 9 for wild type; n = 10, N = 9 for MCU-KO; P = 0.0014, one-tailed Mann Whitney test). (F) Plot illustrating the distribution of normalized mito-GCaMP6 fluorescence over the normalized spike rate in wild-type (gray) and MCU-KO (black) SNc dopaminergic neurons (linear fit and 95% confidence interval, n = 3, N = 2 for wild type; n = 6, N = 6 for MCU-KO). (G) Representative plots of instantaneous CV (continuous traces) and spike rate (dashed traces) for control (gray) and MCU-KO (black) SNc dopaminergic neurons during depolarization steps. (H) Representative 2PLSM image of an SNc dopaminergic neuron expressing mito-roGFP (scale bar, 10 μm). (I) Representative 2PLSM mito-roGFP measurements for wild-type (gray) and MCU-KO (black) SNc neurons expressed as relative oxidation compared to the fully reduced and fully oxidized states obtained upon application of dithiothreitol (DTT; 2 mM) and aldrithiol (Ald; 200 μM), indicated by dashed lines. (J) Quantification of the relative mitochondrial oxidation in wild-type and MCU-KO SNc neurons (n = 12, N = 9 for wild type; n = 9, N = 6 for MCU-KO; P = 0.047, one-tailed Mann-Whitney test). (K) Quantification of the OXPHOS index estimated in wild-type and MCU-KO SNc neurons expressing PercevalHR (n = 5, N = 4 for wild type; n = 5, N = 4 for MCU-KO). (L) Heatmaps of differential expression of genes linked to the antioxidant defense and glutathione (GSH) synthesis, lysosomal function, and mitophagy obtained from RNA-seq analysis from wild-type and MCU-KO SNc neurons expressing RiboTag (N = 8 and 9 for wild type and MCU-KO, respectively). (M) Electron micrographs of identified SNc dopaminergic neurons from wild-type and MCU-KO mice; nuclear membrane is outlined in green, mitochondria are labeled in red; scale bar, 1 μm. (N) Box plots showing no difference in mitochondrial density in wild-type and MCU-KO neurons (n = 23, N = 2; n = 13, N = 2, respectively). Box plots indicate first and third quartiles, thick center lines represent medians, and whiskers indicate the range. *P < 0.05, **P < 0.01.

**Fig. 7.. In MCU-KO neurons, firing is sustained by increased reliance on MAS.**
(A) Cartoon illustrating the pathways through which Ca²⁺ regulates mitochondrial ATP production, either by entering the mitochondrial matrix via MCU and stimulating the TCA cycle or by stimulating the MAS, which can transfer cytosolic reducing equivalents into the mitochondria, where they can be used to fuel OXPHOS; the target of the MAS inhibitor AOAA (5 mM) is indicated. (B) Representative perforated-patch current clamp recording of spontaneous firing in wild-type (top) and MCU-KO (bottom) SNc neurons before and 15 min after bath application of AOAA (5 mM); scale bars, 10 mV, 2 s. (C) Quantification of the effect of 5 mM AOAA on firing on wild-type and MCU-KO SNc neurons (wild type: n = 8, N = 7; MCU-KO: n = 8, N = 5; P = 0.0195, one-tailed Wilcoxon matched-pairs signed rank test). (D) Representative 2PLSM ratio imaging time series showing the effect of bath application of AOAA (5 mM) followed by oligomycin (10 μM) and substitution of glucose with 2-DG on PercevalHR ratio in SNc dopaminergic neurons from wild-type (gray) and MCU-KO (black) neurons. (E) Quantification of the effect of AOAA (5 mM) on ATP/ADP ratio in wild-type and MCU-KO SNc neurons expressing PercevalHR (wild type: n = 5, N = 3; MCU-KO: n = 6, N = 4; P = 0.032, two-tailed Wilcoxon matched-pairs signed rank test). (F) Metabolites significantly changed in SNc tissue from MCU-KO mice versus wild-type mice (N = 5 for each group) identified by volcano plot, with fold change threshold (x axis) 2 and t test threshold (y axis) 0.1. Both fold changes and P values are log-transformed. (G) α-KG levels in wild-type and MCU-KO SNc tissue (N = 5 for each group. ^#Statistical significance is based on (F). Box plots indicate first and third quartiles, thick center lines represent medians, and whiskers indicate the range. *P < 0.05.

**Fig. 8.. Bioenergetic deficiency in MCU-KO neurons relying on a mitochondrial-selective substrate.**
(A) Schematic illustrating the substitution of glucose with mitochondrial substrate β-HB (3.5 mM). (B) Representative perforated-patch recordings of wild-type neurons before and after (15 min) the substrate change. (C) Spike rate in wild-type neurons in glucose and β-HB aCSF (n = 8, N = 8; P = 0.0156, two-tailed Wilcoxon matched-pairs signed rank test). (D) Representative perforated-patch recordings of MCU-KO neurons before and after (15 min) the substrate change. (E) Spike rate in MCU-KO neurons in glucose and β-HB aCSF (n = 7, N = 7). (F) Representative perforated-patch recordings from wild-type (top, gray) and MCU-KO (bottom, black) neurons in β-HB aCSF at the onset and after 4 min of the depolarizing step. (G) Representative plots of normalized spike rate for wild-type (gray) and MCU-KO (black) neurons during the depolarizing step in β-HB aCSF. (H) PercevalHR ratio during the substrate change and depolarizing steps for wild-type (gray) and MCU-KO (black) SNc neurons; medians, range, and individual points are depicted (both n = 7, N = 7). (I) Representative PercevalHR F950 traces for MCU-KO neurons in glucose (gray) and β-HB aCSF (black) upon depolarization step. (J) Drop in PercevalHR F950 upon stimulation in glucose and β-HB aCSF for wild-type and MCU-KO neurons (both n = 6, N = 6; P = 0.0312, two-tailed Wilcoxon matched-pairs signed rank test). (K) Cumulative probability plots of cells spontaneously decreasing spike rate at different time points for wild-type (gray) and MCU-KO (black) neurons during the substrate change and depolarizing steps (both n = 7, N = 7; P = 0.009, Mantel-Cox test). (L) Schematic illustrating how MCU deletion combined with a mitochondria-selective substrate uncovers a bioenergetic deficit in SNc neurons. (B, D, and F) Scale bars, 10 mV, 1 s; dashed gray line, −40 mV. (F to K) Depolarizing steps, 50 pA. Box plots indicate first and third quartiles, thick center lines represent medians, and whiskers indicate the range. *P < 0.05.

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References

1. Attwell D., Laughlin S. B., An energy budget for signaling in the grey matter of the brain. J. Cereb. Blood Flow Metab. 21, 1133–1145 (2001). - PubMed
1. Hall C. N., Klein-Flugge M. C., Howarth C., Attwell D., Oxidative phosphorylation, not glycolysis, powers presynaptic and postsynaptic mechanisms underlying brain information processing. J. Neurosci. 32, 8940–8951 (2012). - PMC - PubMed
1. Le Masson G., Przedborski S., Abbott L. F., A computational model of motor neuron degeneration. Neuron 83, 975–988 (2014). - PMC - PubMed
1. Röper J., Ashcroft F. M., Metabolic inhibition and low internal ATP activate K-ATP channels in rat dopaminergic substantia nigra neurones. Pflugers Arch. 430, 44–54 (1995). - PubMed
1. Hasenstaub A., Otte S., Callaway E., Sejnowski T. J., Metabolic cost as a unifying principle governing neuronal biophysics. Proc. Natl. Acad. Sci. U.S.A. 107, 12329–12334 (2010). - PMC - PubMed

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Ca²⁺ channels couple spiking to mitochondrial metabolism in substantia nigra dopaminergic neurons

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Ca²⁺ channels couple spiking to mitochondrial metabolism in substantia nigra dopaminergic neurons

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