title: 2-Deoxy-D-glucose-induced changes in membrane potential, input resistance, and excitatory postsynaptic potentials of CA1 hippocampal neurons.
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 patch 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 microM 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.
authors.affiliation: Department of Anaesthesia Research, McGill University, Montréal, QC, Canada.
authors.forename: Y T
authors.initials: YT
authors.lastname: Zhao
authors.forename: S
authors.initials: S
authors.lastname: Tekkök
authors.forename: K
authors.initials: K
authors.lastname: Krnjević
mesh_terms: D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology*; D003847:Deoxyglucose / Q000494:pharmacology*; D017097:Electric Impedance; D005905:Glyburide / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000963:Antimetabolites; D007004:Hypoglycemic Agents; C031433:8-(4-sulfophenyl)theophylline; D003847:Deoxyglucose; D013806:Theophylline; D005905:Glyburide