Intracellular Na+ and metabolic modulation of Na/K pump and excitability in the rat suprachiasmatic nucleus neurons

Yi Chi Wang, Jyh Jeen Yang, Rong Chi Huang*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

23 Scopus citations

Abstract

Na/K pump activity and metabolic rate are both higher during the day in the suprachiasmatic nucleus (SCN) that houses the circadian clock. Here we investigated the role of intracellular Na+ and energy metabolism in regulating Na/K pump activity and neuronal excitability. Removal of extracellular K+ to block the Na/K pump excited SCN neurons to fire at higher rates and return to normal K+ to reactivate the pump produced rebound hyperpolarization to inhibit firing. In the presence of tetrodotoxin to block the action potentials, both zero K+ -induced depolarization and rebound hyperpolarization were blocked by the cardiac glycoside strophanthidin. Ratiometric Na imaging with a Na+ -sensitive fluorescent dye indicated saturating accumulation of intracellular Na+ in response to pump blockade with zero K+. The Na+ ionophore monensin also induced Na+ loading and hyperpolarized the membrane potential, with the hyperpolarizing effect of monensin abolished in zero Na+ or by pump blockade. Conversely, Na+ depletion with Na+ -free pipette solution depolarized membrane potential but retained residual Na/K pump activity. Cyanide inhibition of oxidative phosphorylation blocked the Na/K pump to depolarize resting potential and increase spontaneous firing in most cells, and to raise intracellular Na+ levels in all cells. Nonetheless, the Na/K pump was incompletely blocked by cyanide but completely blocked by iodoacetate to inhibit glycolysis, indicating the involvement of both oxidative phosphorylation and glycolysis in fueling the Na/K pump. Together, the results indicate the importance of intracellular Na+ and energy metabolism in regulating Na/K pump activity as well as neuronal excitability in the SCN neurons.

Original languageEnglish
Pages (from-to)2024-2032
Number of pages9
JournalJournal of Neurophysiology
Volume108
Issue number7
DOIs
StatePublished - 01 10 2012

Keywords

  • Intracellular Na
  • Metabolism
  • Na/K pump
  • Suprachiasmatic nucleus

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