Modulation of AMPA excitatory postsynaptic currents in the spinal cord dorsal horn neurons by insulin.
Glutamate AMPA receptors are critical for sensory transmission at the spinal cord dorsal horn (DH). Plasma membrane AMPA receptor endocytosis that can be induced by insulin may underlie long term modulation of synaptic transmission. Insulin receptors (IRs) are known to be expressed on spinal cord DH neurons, but their possible role in sensory transmission has not been studied. In this work the effect of insulin application on fast excitatory postsynaptic currents (EPSCs) mediated by AMPA receptors evoked in DH neurons was evaluated. Acute spinal cord slices from 6 to 10 day old mice were used to record EPSCs evoked in visually identified superficial DH neurons by dorsal root primary afferent stimulation. AMPA EPSCs could be evoked in all of the tested neurons. In 75% of the neurons the size of the AMPA EPSCs was reduced to 62.1% and to 68.9% of the control values when 0.5 or 10 microM insulin was applied. There was no significant change in the size of the AMPA EPSCs in the remaining 25% of DH neurons. The membrane permeable protein tyrosine kinase inhibitor, lavendustin A (10 microM), prevented the insulin induced AMPA EPSC depression. Our results suggest a possible role of the insulin pathway in modulation of sensory and nociceptive synaptic transmission in the spinal cord.
Spicarova
D
D
Department of Functional Morphology, Institute of Physiology, Academy of Sciences of the Czech Republic, Videnska 1083, 14220 Prague 4, Czech Republic.
Palecek
J
J
D000818:Animals; D000831:Animals, Newborn; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D018698:Glutamic Acid / Q000378:metabolism; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D009924:Organ Culture Techniques; D010146:Pain / Q000378:metabolism / Q000503:physiopathology; D018408:Patch-Clamp Techniques; D010636:Phenols / Q000494:pharmacology; D020671:Posterior Horn Cells / Q000187:drug effects / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011972:Receptor, Insulin / Q000187:drug effects / Q000378:metabolism; D018091:Receptors, AMPA / Q000187:drug effects / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D004791:Enzyme Inhibitors; D007328:Insulin; D010636:Phenols; D018091:Receptors, AMPA; D018698:Glutamic Acid; C062898:lavendustin A; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin