Temperature sensitivity of ligand-gated ion channels: ryanodine receptor case

B.I Iaparov,O.E Solovyova,A.S Moskvin

doi:10.1088/1742-6596/929/1/012019

B.I Iaparov, O.E Solovyova + Show 1 more

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https://doi.org/10.1088/1742-6596/929/1/012019

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Abstract

Temperature influences all biochemical processes, in particular, excitation-contraction coupling(ECC) in cardiac cells. In this work we propose a theoretical explanation of temperature effects on an isolated ryanodine receptor calcium release channel (RyR channel) within the electron-conformational (EC) model. We show that the EC model with an Arrhenius-like temperature dependence of the “internal” and “external” frictions and a specific thermosensitivity of the tunnelling “open ↔ closed” transitions can provide both qualitative and quantitative description of the temperature effects for isolated RyR channels. Interestingly that a small change of the activation energy for the “internal” friction can make an ion channel either heat-inhibited or heat-activated while the “external” friction doesn’t play a key role in temperature sensitivity: neglect of “external” friction doesn’t change the channel’s temperature sensitivity qualitatively.

Highlights

Temperature influences all biochemical processes and the excitation-contraction coupling (ECC)in cardiac cells is not a special case
In this work we propose a theoretical explanation of the temperature effects for an isolated ryanodine receptor calcium release channel (RyR channel) within the electronconformational(EC) model
In the paper we focus on an influence of the activation energies EΓ and Eγ on the temperature dependence of the main kinetic characteristics of the ryanodine receptors (RyRs) channel gating, such as open time probability, Popen, mean open and mean closed times, htopen i and htclose i, respectively

Summary

Introduction

Temperature influences all biochemical processes and the excitation-contraction coupling (ECC)in cardiac cells is not a special case. Temperature influences all biochemical processes and the excitation-contraction coupling (ECC). Experiments [1] show, that hypothermia increases action potential duration, intracellular Ca2+ transients and muscle contraction amplitude. The key elements of ECC are ryanodine receptors (RyRs), the ligand gated ion channels which govern the Ca2+ release from sarcoplasmic reticulum (SR), intracellular calcium storage. RyR gating leads to cardiac arrhythmias and heart failure [2], the understanding the RyR gating is mandatory in order to understand the excitation-contraction coupling. According to single RyR channel patch clamp experiments [3], the RyR channel gating changes significantly with temperature. From the viewpoint of the condensed matter physics it seems to be absolutely inexplicable how the ≈ 6 % change in absolute temperature can produce manyfold effect in the channel activity. How can the temperature sensitivity of the RyR channel’s gating be so high?

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