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- W1914405346 abstract "The spatiotemporal characteristics of NMDA receptor-mediated changes in intracellular calcium ([Ca2+]i) (NMDAR-[Ca2+]i) is critical in determining the strength of NMDA effects on neuronal excitability. Here we investigated the role mitochondria in shaping NMDAR-[Ca2+]i dynamics. We activated NMDARs before and after the mitochondrial uncoupler CCCP (10µM for 10 sec), which prevents [Ca2+]i uptake by disruption of the proton gradient across the mitochondrial inner membrane. In both, identified and non-identified eGFP-VP SON neurons, focal application of NMDA (10µM for 1 sec) following CCCP resulted in a significantly larger and slower Δ[Ca2+]i response both in soma and dendrites, and a more robust membrane depolarization and firing discharge compared to the control application. Conversely, a similar underlying NMDAR-mediated current (INMDA) was observed. Direct depolarization of SON neurons by current injection (0.15 nA for 2 sec) was used to evoke a similar number of action potentials and associated increase in [Ca2+]I as those evoked NMDAR activation. In this condition however, CCCP failed to potentiate the action potential-evoked Δ[Ca2+]i response. Moreover In slices preincubated with Ru360 (10 µM, 30 min), a selective and potent inhibitor of the mitochondrial Ca2+ uptake uniporter, subsequent application of CCCP failed to potentiate the NMDA-[Ca2+]i response. Taken together, our study support the hypothesis that mitochondria play a critical role in regulating NMDA-[Ca2+]i dynamics, and therefore, the degree of membrane excitability and firing activity of MNC neurons following NMDAR activation. Grant Funding Source: NIH HL090948-2" @default.
- W1914405346 created "2016-06-24" @default.
- W1914405346 creator A5026242337 @default.
- W1914405346 creator A5082439762 @default.
- W1914405346 date "2014-04-01" @default.
- W1914405346 modified "2023-09-27" @default.
- W1914405346 title "Mitochondria influence NMDA‐induced calcium dynamics in hypothalamic magnocellular neurosecretary cells (686.28)" @default.
- W1914405346 doi "https://doi.org/10.1096/fasebj.28.1_supplement.686.28" @default.
- W1914405346 hasPublicationYear "2014" @default.
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