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The Ca²⁺ permeation mechanism of the ryanodine receptor revealed by a multi-site ion model.

ABSTRACT: Ryanodine receptors (RyR) are ion channels responsible for the release of Ca²⁺ from the sarco/endoplasmic reticulum and play a crucial role in the precise control of Ca²⁺ concentration in the cytosol. The detailed permeation mechanism of Ca²⁺ through RyR is still elusive. By using molecular dynamics simulations with a specially designed Ca²⁺ model, we show that multiple Ca²⁺ ions accumulate in the upper selectivity filter of RyR1, but only one Ca²⁺ can occupy and translocate in the narrow pore at a time, assisted by electrostatic repulsion from the Ca²⁺ within the upper selectivity filter. The Ca²⁺ is nearly fully hydrated with the first solvation shell intact during the whole permeation process. These results suggest a remote knock-on permeation mechanism and one-at-a-time occupation pattern for the hydrated Ca²⁺ within the narrow pore, uncovering the basis underlying the high permeability and low selectivity of the RyR channels.

SUBMITTER: Zhang A

PROVIDER: S-EPMC7026163 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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The Ca2+ permeation mechanism of the ryanodine receptor revealed by a multi-site ion model.

Zhang Aihua A Yu Hua H Liu Chunhong C Song Chen C

Nature communications 20200217 1

Ryanodine receptors (RyR) are ion channels responsible for the release of Ca2+ from the sarco/endoplasmic reticulum and play a crucial role in the precise control of Ca2+ concentration in the cytosol. The detailed permeation mechanism of Ca2+ through RyR is still elusive. By using molecular dynamics simulations with a specially designed Ca2+ model, we show that multiple Ca2+ ions accumulate in the upper selectivity filter of RyR1, but only o ...[more]

PMID: 32066742

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