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Multi-ion versus single-ion conduction mechanisms can yield current rectification in biological ion channels

Abstract

There is clear evidence that the net magnitude of negative charge at the intracellular end of inwardly rectifying potassium channels helps to generate an asymmetry in the magnitude of the current that will pass in each direction. However, a complete understanding of the physical mechanism that links these charges to current rectification has yet to be obtained. Using Brownian dynamics, we compare the conduction mechanism and binding sites in rectifying and non-rectifying channel models. We find that in our models, rectification is a consequence of asymmetry in the hydrophobicity and charge of the pore lining. As a consequence, inward conduction can occur by a multi-ion conduction mechanism. However, outward conduction is restricted, since there are fewer ions at the intracellular entrance and outwardly moving ions must cross the pore on their own. We pose the question as to whether the same mechanism could be at play in inwardly rectifying potassium channels.

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Acknowledgments

Silvie Ngo provided excellent technical assistance, for which we are grateful. We thank Michael Thomas for his scientific advice. This work was supported by the NCI National Facility at the Australian National University. We gratefully acknowledge the support from the Australian Research Council through a Discovery Early Career Researcher Award, and the National Health and Medical Council.

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Correspondence to Tamsyn A. Hilder.

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Hilder, T.A., Corry, B. & Chung, SH. Multi-ion versus single-ion conduction mechanisms can yield current rectification in biological ion channels. J Biol Phys 40, 109–119 (2014). https://doi.org/10.1007/s10867-013-9338-4

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  • DOI: https://doi.org/10.1007/s10867-013-9338-4

Keywords

  • Kir channels
  • Transmembrane domain
  • Binding sites
  • Brownian dynamics
  • Rectification mechanism