Counterion-assisted cation transport in a biological calcium channel

The Journal of Physical Chemistry. B
Hao DongGiacomo Fiorin

Abstract

How ions pass through the lumen of an ion channel is a key question underlying cellular communication. The effects of water and pore-lining residues (channel design) have been extensively explored. However, the role of counterions is less well understood. The pore subunit of the calcium release-activated calcium channel, Orai, provides a useful model to explore the effect of anions on the permeation of cations. Herein, we employ computer simulations molecular dynamics (MD) to explore ion permeation through the V174A Orai mutant, a constitutively open pore, in a phospholipid membrane hydrated by a 150 mM NaCl solution. When an external voltage is applied in the MD simulations, it induces only a moderate conformational change to the channel, which facilitates the passage of ions. Infrequent sodium permeation is observed on the microsecond time scale, which is consistent with experiment. In contrast, the chloride counterions exhibit higher mobility in the channel and are actively involved in sodium transport. The anion-assisted cation permeation identified here likely highlights a more general functional role for counterions, especially in ion channels with medium pore-size. Experiments with a variety of counterions might further ...Continue Reading

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Citations

May 16, 2018·Proceedings of the National Academy of Sciences of the United States of America·Priscilla S-W YeungMurali Prakriya
Apr 6, 2019·The Journal of Physiology·Priscilla See-Wai YeungMurali Prakriya
Mar 27, 2015·The Journal of Physiology·I Llorente-FolchJ Satrustegui
Dec 10, 2019·The Journal of General Physiology·Megumi YamashitaMurali Prakriya
Sep 25, 2015·Physiological Reviews·Murali Prakriya, Richard S Lewis

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