Insulin-like growth factor I potentiates kainate receptors through a phosphatidylinositol 3-kinase dependent pathway.
Neurotrophic factors modulate synaptic plasticity through mechanisms that include regulation of membrane ion channels and neurotransmitter receptors. Recently, it was shown that insulin-like growth factor I (IGF-I) induces depression of AMPA-mediated currents without affecting NMDA-receptor function in neurons. We now report that IGF-I markedly potentiates the kainate-preferring ionotropic glutamate receptor in young cerebellar granule neurons expressing functional kainate-, but not AMPA-mediated currents. Potentiation of kainate responses by IGF-I is blocked by wortmannin, a phosphatidylinositol 3-kinase (P13K) inhibitor, indicating a role for this kinase in the effect of IGF-I. These results reinforce the notion that modulation of ionotropic glutamate receptors are involved in the regulatory actions of IGF-I on neuronal plasticity.
Gonzalez de la Vega
A
A
Cajal Institute, CSIC, Avda. Dr. Arce 37, 28002 Madrid, Spain.
Buño
W
W
Pons
S
S
Garcia-Calderat
M S
MS
Garcia-Galloway
E
E
Torres-Aleman
I
I
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D018092:Kainic Acid Receptors / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D000077191:Wortmannin
D000730:Androstadienes; D004791:Enzyme Inhibitors; D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases; D018092:Kainic Acid Receptors; D000077191:Wortmannin