2-Deoxy-D-glucose-induced changes in membrane potential, input resistance, and excitatory postsynaptic potentials of CA1 hippocampal neurons

Y. T. Zhao, S. Tekkök, K. Krnjević

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

Temporary block of glycolysis by 2-deoxy-D-glucose (2-DG) reversibly suppresses synaptic transmission in the CA1 region of hippocampal slices. Recovery of responses is followed by a sustained potentiation of field excitatory postsynaptic potentials (EPSPs) (2-DG-LTP). To investigate the mechanisms involved in this type of LTP, we studied the effects of 2-DG on membrane properties of CA1 neurons (in slices from Sprague-Dawley rats), recorded with sharp intracellular electrodes containing 3 M KCl, as well as parch electrodes, filled mainly with 150 mM KMeSO4 and Hepes. The predominant change produced by 15- to 20-min applications of 2-DG (10 mM, replacing glucose) was hyperpolarization (-5.6 ± 1.1 mV for 18 intracellular recordings and -7.2 ± 0.80 mV for 17 whole-cell recordings) accompanied by a fall in resistance (-33 ± 2.5% for 14 intracellular recordings and -11.6 ± 7.1% for 15 whole-cell recordings). Virtually identical hyperpolarizations were recorded in the presence of 20 μM glyburide (-5.5 ± 1.5 mV n = 6), but they were abolished by adenosine antagonists 8-(p-sulfophenyl)theophylline (8-SPT) and 8-cyclopentyl-3,7-dihydro-1,3-dipropyl-1H-purine-2,6-dione (DPCPX) (2.8 ± 1.6 and 4.0 ± 1.7 mV, respectively; n = 5 for both). It was concluded that the hyperpolarization is most likely caused by an increase in K+ conductance, activated by a 2-DG induced rise in adenosine release. After such applications of 2-DG, a sustained potentiation of EPSPs (similar to the 2-DG-LTP of field EPSPs) was evident in five neurons recorded with intracellular electrodes but not in any of nine whole-cell recordings, where it was replaced by sustained, LTD-like depression. We conclude that a factor essential for 2-DG-LTP induction is lost during whole-cell recording.

Original languageEnglish (US)
Pages (from-to)368-374
Number of pages7
JournalCanadian Journal of Physiology and Pharmacology
Volume75
Issue number5
DOIs
StatePublished - 1997
Externally publishedYes

Keywords

  • 2-Deoxyglucose
  • 8-(p-sulfophenyl)theophylline (8-SPT)
  • 8-Cyclopentyl-3,7-dihydro-1,3-dipropyl-1H-purine-2,6-dione (DPCPX)
  • Ca-activated K channels
  • Glyburide
  • Hyperpolarization
  • Long-term depression
  • Long-term potentiation

ASJC Scopus subject areas

  • Physiology
  • Pharmacology
  • Physiology (medical)

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