Heparin modulates the single channel kinetics of reconstituted AMPA receptors from rat brain

Glutamate receptors specifically activated by alpha-amino-3-hydroxydmethyli soxazole-4-propionic acid (AMPA) have been reported to interact with the hi ghly sulfated glycosaminoglycan, heparin, and to subsequently express lower binding affinity for [H-3]AMPA. The present study examined whether heparin also modifies the kinetic properties of single channel activity expressed by isolated AMPA receptors from rat forebrain. Upon application of 280 nM A MPA, the partially purified receptors reconstituted in lipid bilayers expre ssed bursting channel activity that was inhibited by dinitroquinoxaline-2-3 ,-dione (DNQX). Treating the receptors with heparin (10 mu g/ml) produced n o change in conductance but the mean burst length for 280 nM AMPA was nearl y doubled. Heparin also prolonged the lifetime of open states of the indivi dual ion channels 3-5-fold, perhaps by causing a decrease in the closing ra te constant for channel gating. Heparin had no effect on the lifetime of th e closed state or on the amplitude of currents. The single channel open tim e was voltage-dependent and an increase of applied voltage caused a decreas e in the heparin effect on channel open times. While the lifetime of the op en channel was increased 3-4 times by heparin at 20 mV, there was no signif icant change induced at 43 mV. The equivalent electric charge of the channe l gate was increased by 40%. The heparin effects were specific as another p olysaccharide, dextran, and a monomeric constituent of heparin, glucosamine 2,3-disulfate, failed to have any effect on the receptors. These findings suggest that heparin-containing extracellular matrix components can interac t with AMPA receptors and influence their functional properties. Synapse 31 :203-209, 1999. (C) 1999 Wiley-Liss, Inc.