Elucidating the molecular details underlying charge-selectivity in pentameric Ligand Gated Ion Channels

Claudio Grosman, University of Illinois at Urbana-Champaign

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Pentameric Ligand-Gated Ion Channels (pLGICs) are a superfamily of ion channels responsible for neuronal signaling. Although neurotransmitter-gated ion channels are abundant in the nervous system, pLGICs—in particular—are unique in that they are the only superfamily of neurotransmitter-gated ion channels that contains both highly cation- and highly anion-selective receptors. Cation-versus-anion selectivity, or charge selectivity, is critical for the proper function of the nervous system. In resting adult neurons, cation-selective receptors are excitatory in that they stimulate action potentials while anion-selective receptors are inhibitory because they suppress action potentials. pLGICs are the only superfamily of neurotransmitter-gated ion channels that contain anion-selective receptors, and therefore, pLGICs are the only source of neurotransmitter gated synaptic inhibition. Given that cation- and anion-selective pLGICs are similar in sequence, they provide a prototypical model for understanding molecular origins of charge selectivity. Although experiments can characterize the selectivity of an ion channel, only detailed computer simulations can provide the necessary resolution to delineate the molecular details that underlie charge selectivity.