FACILITATION OF CURRENTS THROUGH RAT CA2-PERMEABLE AMPA RECEPTOR CHANNELS BY ACTIVITY-DEPENDENT RELIEF FROM POLYAMINE BLOCK()

1. In outside-out patches excised from human embryonic kidney (HEK) 29 3 cells expressing Ca2+-permeable ha-amino-3-hydroxy-5-methyl-4-isoxaz ole-propionate receptor (AMPAR) channels, currents activated by 1 ms g lutamate pulses at negative membrane potentials facilitated during and following a repetitive (2 to 100 Hz) agonist application. The degree of facilitation depended on subunit type, membrane potential and stimu lation frequency being antagonized by a slow recovery from desensitiza tion. 2. Activity-dependent current facilitation occurred in Ca2+-perm eable but not in Ca2+-impermeable AMPAR channels. Current facilitation , however, does not depend on Ca2+ flux. Rather it reflects a relief f rom the block of Ca2+-permeable AMPARs by intracellular polyamines sin ce facilitation occurred only in the presence of polyamines and since facilitated currents had a nearly linear current-voltage relation (I-V ). 3. Relief from polyamine block was use dependent and occurred mainl y in open channels. The relief mechanism was determined primarily by m embrane potential rather than by current flow 4. In closed channels th e degree of polyamine block was independent of membrane potential. The voltage dependence of the rate of relief from the block in open chann els rather than the voltage dependence of the block underlies the inwa rdly rectifying shape of the I-V at negative potentials. 5. Currents t hrough native Ca2+-permeable AMPAR channels in outside-out or nucleate d patches from either hippocampal basket cells or a subtype of neocort ical layer II nonpyramidal cells also showed facilitation. 6. It is co ncluded that a use-dependent relief from polyamine block during consec utive AMPAR channel openings underlies current facilitation. This poly amine-AMPAR interaction may represent a new activity-dependent postsyn aptic mechanism for control of synaptic signalling.