Figure 1.

Insulin potentiates NMDA whole-cell currents. (A) A typical sequence showing NMDA-activated whole-cell currents recorded at V_h = −60 mV from oocytes expressing NR1–4a/NR2A receptors before and after application of insulin (1 μM, 10 min). NMDA, 300 μM; glycine, 10 μM. Insulin potentiated NMDA-elicited currents to 2.8 ± 0.1 (n = 11) times control. (B) The oocytes expressing NR1–4a/NR2A receptors were preincubated at least 1 h in control external solution, containing the nonselective inhibitor of tyrosine kinases, genistein (100 μM). Genistein had no effect on either basal NMDA responses or insulin potentiation. Potentiation was to 2.7 ± 0.2 (n = 3) after preincubation of oocytes in genistein. (C) Tyrphostin A47 (100 μM; 10 min), a selective inhibitor of insulin receptor tyrosine kinases, slightly potentiated the control NMDARs current (to 1.56 ± 0.16 times control), but completely blocked insulin potentiation of NMDA-elicited currents. Insulin potentiation was to 1.02 ± 0.10 times the control NMDA response in the presence of tyrphostin alone. (D) Summary of experiments showing potentiation of NMDA currents by insulin in the absence and presence of genistein and tyrphostin A47.