Stargazin attenuates intracellular polyamine block of calcium-permeable AMPA receptors

• Published in: Nature neuroscience Vol. 10; no. 10; pp. 1260 - 1267
• Main Authors: Soto, David, Coombs, Ian D, Cull-Candy, Stuart G, Farrant, Mark, Kelly, Leah
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.10.2007
• Subjects: Age Factors; Animals; Animals, Newborn; Calcium - metabolism; Calcium Channels - physiology; Cell receptors; Cerebellum - cytology; Dose-Response Relationship, Radiation; Electric Stimulation; Excitatory Postsynaptic Potentials - drug effects; Excitatory Postsynaptic Potentials - physiology; Excitatory Postsynaptic Potentials - radiation effects; Glutamic Acid - pharmacology; Humans; In Vitro Techniques; Ion Channel Gating - drug effects; Ion Channel Gating - physiology; Ion channels; Membrane Potentials - drug effects; Membrane Potentials - physiology; Membrane Potentials - radiation effects; Neurons - drug effects; Neurons - physiology; Patch-Clamp Techniques - methods; Physiological aspects; Polyamines; Polyamines - pharmacology; Rats; Rats, Sprague-Dawley; Receptors, AMPA - physiology; Receptors, Glutamate - drug effects; Receptors, Glutamate - physiology; Spermine - pharmacology; Transfection; United Kingdom
• ISSN: 1097-6256; 1546-1726
• DOI: 10.1038/nn1966

Endogenous polyamines profoundly affect the activity of various ion channels, including that of calcium-permeable AMPA-type glutamate receptors (CP-AMPARs). Here we show that stargazin, a transmembrane AMPAR regulatory protein (TARP) known to influence transport, gating and desensitization of AMPARs, greatly reduces block of CP-AMPARs by intracellular polyamines. By decreasing CP-AMPAR affinity for cytoplasmic polyamines, stargazin enhances the charge transfer following single glutamate applications and eliminates the frequency-dependent facilitation seen with repeated applications. In cerebellar stellate cells, which express both synaptic CP-AMPARs and stargazin, we found that the rectification and unitary conductance of channels underlying excitatory postsynaptic currents were matched by those of recombinant AMPARs only when the latter were associated with stargazin. Taken together, our observations establish modulatory actions of stargazin that are specific to CP-AMPARs, and suggest that during synaptic transmission the activity of such receptors, and thus calcium influx, is fundamentally changed by TARPs.