Temporary (10-20 min) replacement of glucose in the perfusion medium with 2-deoxy-D-glucose (2-DG) causes a marked and sustained potentiation of excitatory synaptic transmission in CA1 hippocampus (Tekkök & Krnjevic, 1995). Intracellular sharp microelectrode recordings have shown that 2-DG induces hyperpolarization accompanied by an increase in input resistance (Krnjevic & Zhao, 2000). We performed whole-cell and perforated patch-clamp experiments on CA1 pyramidal neurones and investigated the effects of 2-DG on baseline holding current (I_BH) and input conductance (G_N). Transverse hippocampal slices were prepared from Male Wistar rats (100Ð120 g) and kept submerged at 34 °C (animals were humanely killed according to UK legislation). Electrodes were filled with a solution containing (mM): KMeSO₄ (118), KCl (18), Hepes (10), EGTA (1), CaCl₂ (0.1), Mg-ATP (2-10), Na-GTP (0.3) and NaCl (8). In some experiments K₂-creatine phosphate (20 mM) and phosphocreatine kinase (50 U l^-1) were also added (ATP regenerating solution). In 17 cells clamped at -60 mV replacement of glucose in perfusion medium with 2-DG (10 mM for 15 min) resulted in an inward shift in I_BH (-1330 ± 120 pA, mean ± S.E.M.) and an increase in G_N (75 ± 11 %) (P < 0.001). These changes in I_BH and G_N did not recover upon perfusion with glucose-containing saline for 45 min (n = 9). In ten cells glucose was replaced with sucrose (10 mM) and similar effects on I_BH (-1470 ± 230 pA) and G_N (84 ± 26 %) were observed (P < 0.001). Increasing ATP concentration in the electrode filling solution to 10 mM (n = 7) or recording with ATP regenerating solution (n = 5) did not affect the 2-DG-induced changes in I_BH and G_N. In 12 cells recorded with amphotericin B-containing electrode filling solution (perforated patch) 2-DG induced similar changes in I_BH (-1240 ± 170 pA) and G_N (88 ± 14 %) (P < 0.001). A cocktail of glutamate receptor antagonists containing (mM): D(-)-amino-5-phosphonopentanoic acid (50), 7-chlorokynurenate (100), MK-801 (50) and 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzol[f]quinoxaline-7-sulphonamide (50) depressed the 2-DG effects on I_BH (-260 ± 30 pA) and G_N (12 ± 4 %) (n = 9) (P < 0.01). These results suggest that excessive glutamate accumulation may be responsible for the 2-DG-induced changes in I_BH and G_N in cells recorded in whole-cell or perforated patch-clamp mode.

All procedures accord with current UK legislation.