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Macroscopic Kinetics of Pentameric Ligand Gated Ion Channels: Comparisons between Two Prokaryotic Channels and One Eukaryotic Channel

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  • Kurt T Laha
  • Borna Ghosh
  • Cynthia Czajkowski

Abstract

Electrochemical signaling in the brain depends on pentameric ligand-gated ion channels (pLGICs). Recently, crystal structures of prokaryotic pLGIC homologues from Erwinia chrysanthemi (ELIC) and Gloeobacter violaceus (GLIC) in presumed closed and open channel states have been solved, which provide insight into the structural mechanisms underlying channel activation. Although structural studies involving both ELIC and GLIC have become numerous, thorough functional characterizations of these channels are still needed to establish a reliable foundation for comparing kinetic properties. Here, we examined the kinetics of ELIC and GLIC current activation, desensitization, and deactivation and compared them to the GABAA receptor, a prototypic eukaryotic pLGIC. Outside-out patch-clamp recordings were performed with HEK-293T cells expressing ELIC, GLIC, or α1β2γ2L GABAA receptors, and ultra-fast ligand application was used. In response to saturating agonist concentrations, we found both ELIC and GLIC current activation were two to three orders of magnitude slower than GABAA receptor current activation. The prokaryotic channels also had slower current desensitization on a timescale of seconds. ELIC and GLIC current deactivation following 25 s pulses of agonist (cysteamine and pH 4.0 buffer, respectively) were relatively fast with time constants of 24.9±5.1 ms and 1.2±0.2 ms, respectively. Surprisingly, ELIC currents evoked by GABA activated very slowly with a time constant of 1.3±0.3 s and deactivated even slower with a time constant of 4.6±1.2 s. We conclude that the prokaryotic pLGICs undergo similar agonist-mediated gating transitions to open and desensitized states as eukaryotic pLGICs, supporting their use as experimental models. Their uncharacteristic slow activation, slow desensitization and rapid deactivation time courses are likely due to differences in specific structural elements, whose future identification may help uncover mechanisms underlying pLGIC gating transitions.

Suggested Citation

  • Kurt T Laha & Borna Ghosh & Cynthia Czajkowski, 2013. "Macroscopic Kinetics of Pentameric Ligand Gated Ion Channels: Comparisons between Two Prokaryotic Channels and One Eukaryotic Channel," PLOS ONE, Public Library of Science, vol. 8(11), pages 1-9, November.
  • Handle: RePEc:plo:pone00:0080322
    DOI: 10.1371/journal.pone.0080322
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    References listed on IDEAS

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    1. Nicolas Bocquet & Hugues Nury & Marc Baaden & Chantal Le Poupon & Jean-Pierre Changeux & Marc Delarue & Pierre-Jean Corringer, 2009. "X-ray structure of a pentameric ligand-gated ion channel in an apparently open conformation," Nature, Nature, vol. 457(7225), pages 111-114, January.
    2. Nicolas Bocquet & Lia Prado de Carvalho & Jean Cartaud & Jacques Neyton & Chantal Le Poupon & Antoine Taly & Thomas Grutter & Jean-Pierre Changeux & Pierre-Jean Corringer, 2007. "A prokaryotic proton-gated ion channel from the nicotinic acetylcholine receptor family," Nature, Nature, vol. 445(7123), pages 116-119, January.
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