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

David Papke, Giovanni Gonzalez-Gutierrez, Claudio Grosman

Research output: Contribution to journalArticlepeer-review

Abstract

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. Abstract Changes in synaptic strength allow synapses to regulate the flow of information in the neural circuits in which they operate. In particular, changes lasting from milliseconds to minutes ('short-term changes') underlie a variety of computational operations and, ultimately, behaviours. Most studies thus far have attributed the short-term type of plasticity to activity-dependent changes in the dynamics of neurotransmitter release (a presynaptic mechanism) while largely dismissing the role of the loss of responsiveness of postsynaptic receptor channels to neurotransmitter owing to entry into desensitization. To better define the response of the different neurotransmitter-gated ion channels (NGICs) to repetitive stimulation without interference from presynaptic variables, we studied eight representative members of all three known superfamilies of NGICs in fast-perfused outside-out patches of membrane. We found that the responsiveness of all tested channels (two nicotinic acetylcholine receptors, two glycine receptors, one GABA receptor, two AMPA-type glutamate receptors and one purinergic receptor) declines along trains of brief neurotransmitter pulses delivered at physiologically relevant frequencies to an extent that suggests that the role of desensitization in the synaptic control of action-potential transmission may be more general than previously thought. Furthermore, our results indicate that a sizable fraction (and, for some NGICs, most) of this desensitization occurs during the neurotransmitter-free interpulse intervals. Clearly, an incomplete clearance of neurotransmitter from the synaptic cleft between vesicle-fusion events need not be invoked to account for NGIC desensitization upon repetitive stimulation.

Original languageEnglish (US)
Pages (from-to)1571-1585
Number of pages15
JournalJournal of Physiology
Volume589
Issue number7
DOIs
StatePublished - Apr 2011

ASJC Scopus subject areas

  • Physiology

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