Electrodiffusion of synaptic receptors: a mechanism to modify synaptic efficacy?

We analysed physical forces that act on synaptic receptor-channels following the release of neurotransmitter. These forces are: 1) electrostatic interaction between receptors, 2) stochastic Brownian diffusion in the membrane, 3) transient electric field force generated by currents through open channels, 4) viscous drag force elicited by the flowing molecules and 5) strong in-membrane friction. By considering alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) type receptors, we show that, depending on the size and electrophoretic charge of the extracellular receptor domain, release of an excitatory neurotransmitter (glutamate) can induce receptor clustering towards the release site on a fast time scale (8-100 ms). This clustering progresses whenever repetitive synaptic activation exceeds a critical frequency (20-100 s(-1), depending on the currents through individual channels). As a result, a higher proportion of the receptors is exposed to higher glutamate levels. This should increase by 50-100% the peak synaptic current induced by the same amount of released neurotransmitter. In order for this mechanism to contribute to long-term changes of synaptic efficacy, we consider the possibility that the in-membrane motility of the AMPA receptors is transiently increased during synaptic activity, e. g., through the breakage of receptor anchors in the postsynaptic membrane due to activation of N-methyl-d-aspartic acid receptors.