Reduction in mitochondrial ATP synthesis mimics the effect of low glucose in depolarizing neurons from the subpostremal nucleus of the solitary tract of rats.

Publisher: Springer Country of Publication: United States NLM ID: 7701859 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1573-6881 (Electronic) Linking ISSN: 0145479X NLM ISO Abbreviation: J Bioenerg Biomembr Subsets: MEDLINE

Publication: 1999- : New York, NY : Springer
Original Publication: New York, Plenum Press.

Glucose*/metabolism ; Glucose*/pharmacology ; Adenosine Triphosphate*/metabolism ; Adenosine Triphosphate*/biosynthesis ; Neurons*/metabolism ; Neurons*/drug effects ; Solitary Nucleus*/metabolism ; Solitary Nucleus*/drug effects ; Mitochondria*/metabolism ; Mitochondria*/drug effects; Animals ; Rats ; Male ; Membrane Potentials/drug effects

Neurons of the subpostremal nucleus of the solitary tract (NTS) respond to changes in extracellular glucose with alterations in membrane potential with both depolarization and hyperpolarization. From 5 mM glucose, a rapid shift to 0.5 mM glucose produces a membrane depolarization by an unknown mechanism in most neurons. However, the mechanism involved in this response needs to be known. Here, we investigated if the low glucose-induced depolarization could be mimicked by reducing ATP synthesis and possible mediators of this effect. We showed that applying the mitochondrial uncoupler CCCP (1 µM) reproduced the effects of low glucose depolarizing the membrane, generating an inward current, and decreasing membrane resistance. On the other hand, activation of AMPK did not alter these parameters. To test if low glucose and CCCP could depolarize the membrane by affecting the ionic gradient, we inhibited the electrogenic Na/K pump with 10 µM of ouabain. We observed a similar membrane depolarization but not a decrease in membrane resistance. We conclude that perfusion of neurons of the subpostremal NTS with a low glucose solution depolarizes the membrane by probably reducing intracellular ATP, but not by activating AMPK or decreasing the ionic gradient across the membrane.
(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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2022/14196-3 Fundação de Amparo à Pesquisa do Estado de São Paulo

Keywords: ATP; Glycemia; Mitochondria; NTS

IY9XDZ35W2 (Glucose)
8L70Q75FXE (Adenosine Triphosphate)

Date Created: 20240912 Date Completed: 20241005 Latest Revision: 20241005

20241006

10.1007/s10863-024-10037-8

39266925