Desensitization of neurotransmitter‐gated ion channels during high‐frequency stimulation: a comparative study of Cys‐loop, AMPA and purinergic receptors

Abstract

Non‐technical summary During fast synaptic transmission, series of brief pulses of highly concentrated neurotransmitter impinge repetitively on the postsynaptic membrane. The number of neurotransmitter‐gated ion channels (NGICs) that open in response to each neurotransmitter pulse may increase or decrease along such trains of stimuli to an extent that can affect the transmission of action potentials. This ‘short‐term’ plasticity results from transient changes (lasting from milliseconds to minutes) in the properties of the presynaptic terminal, the postsynaptic terminal, or both. In this paper, we studied eight representative members of all three known superfamilies of NGICs to determine the extent to which short‐term plasticity can occur at the postsynaptic‐receptor level. We found that the responsiveness of all tested channels declines appreciably along trains of brief neurotransmitter pulses delivered at physiologically relevant frequencies. We suggest that the role of receptor desensitization in the synaptic control of action‐potential transmission may be more general than previously thought.