FIGURE 1.

(A) Schematic drawing of events underlying polyamine dependent facilitation of CP-AMPARs. In the closed state most of the channels are blocked by intracellular polyamines (A1). Repetitive activation of CP-AMPARs at negative potentials either by a train of brief glutamate applications or by mediator released in response to the train of action potentials, leads to progressive relief from the block and enhancement of AMPAR-mediated current amplitudes (A2). (B) Factors determining amplitudes of the currents through CP-AMPARs during high frequency activation. The blue trace shows a hypothetical response to a train of glutamate applications without contribution of channel desensitization and polyamine dependent facilitation. Experimentally this can be achieved in the presence of cyclothiazide and after washout of intracellular polyamines. Contribution of polyamine dependent facilitation (no channel desensitization) is depicted by the black trace. Note the strong impact of the polyamine block on the first response amplitude. The red trace shows gradual reduction of AMPAR-mediated currents due to channel desensitization in the absence of polyamine dependent facilitation. The green trace illustrates the product of interplay between channel desensitization and polyamine dependent facilitation of CP-AMPARs. The final amplitude dynamics in every given case will depend on: desensitization time constants, polyamine concentration and stimulation frequency.