The inositol trisphosphate receptor (IPR) is a crucial Ca^{2+ channel that regulates the Ca^{2+} influx from the endoplasmic reticulum (ER) to the cytoplasm. A thorough study of this receptor contributes to a better understanding of calcium oscillations and waves. Based on the patch-clamp experimental data obtained from the outer membranes of isolated nuclei of theXenopus oocyte, we construct an allosteric competition model of single IPR channels on their native ER membrane environment. In our model, each IPR channel consists of four subunits, each of which can exist in two configurations. Each subunit in both configurations has one IP_3 binding site, together with one activating and one inhibitory Ca^{2+ the well-known Monod-Wyman-Changeux allosteric model, we construct our model from the subunit level to the channel level  . It turns out that our model successfully reproduces the patch-clamp experimental data of the steady-state open probability, the mean close duration, and the bi-exponential distribution of the open duration . Particularly, our model successfully describes the  bimodal [Ca^{2+}] dependence of the mean open duration at high [IP_3], a steady-state behavior which fails to be correctly described in previous IPR models , and the adaptation of the IPR channel, an important dynamic behavior which is seldom discussed in previous IPR models. In addition, we find that the gating of the IPR channel is most likely to be a biochemical process that consumes energy.
The inositol trisphosphate receptor (IPR) is a crucial ion channel that regulates the Ca^{2+} influx from the endoplasmic reticulum (ER) to the cytoplasm. A thorough study of the IPR channel contributes to a better understanding of calcium oscillations and waves. It has long been observed that the IPR channel is a typical biological system which performs adaptation. However, recent advances on the physical essence of adaptation show that adaptation systems with a negative feedback mechanism, such as the IPR channel, must break detailed balance and always operate out of equilibrium with energy dissipation. Almost all previous IPR models are equilibrium models assuming detailed balance and thus violate the physical essence of adaptation. In this article, we constructed a nonequilibrium allosteric model of single IPR channels based on the patch-clamp experimental data obtained from the IPR in the outer membranes of isolated nuclei of theXenopus oocyte . It turns out that our model reproduces the patch-clamp experimental data reasonably well and produces both the correct steady-state and dynamic properties of the channel . Particularly, our model successfully describes the complicated bimodal [Ca^{2+}] dependence of the mean open duration at high [IP_3], a steady-state behavior which fails to be correctly described in previous IPR models . Finally, we used the patch-clamp experimental data to validate that the IPR channel indeed breaks detailed balance and thus is a nonequilibrium system which consumes energy.
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Ca^{2+
ion
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this receptor
the IPR channel
D
Based on the patch-clamp experimental data obtained from the outer membranes of isolated nuclei of the
D
Xenopus
R
oocyte, we construct an allosteric competition
It has long been observed that the IPR channel is a typical biological system which performs adaptation. However, recent advances on the physical essence of adaptation show that adaptation systems with a negative feedback mechanism, such as the IPR channel, must break detailed balance and always operate out of equilibrium with energy dissipation. Almost all previous IPR models are equilibrium models assuming detailed balance and thus violate the physical essence of adaptation. In this article, we constructed a nonequilibrium allosteric
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on their native ER membrane environment. In our model, each IPR channel consists of four subunits, each of which can exist in two configurations. Each subunit in both configurations has one IP_3 binding site, together with one activating and one inhibitory Ca^{2+
based on
R
well-known Monod-Wyman-Changeux allosteric model, we construct our model from the subunit level to the channel level
patch-clamp experimental data obtained from the IPR in the outer membranes of isolated nuclei of the
A
Xenopus
A
oocyte
D
successfully
R
of the
reasonably well and produces both the correct
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open probability, the mean close duration, and the bi-exponential distribution of the open duration
and dynamic properties of the channel
A
complicated
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, and the adaptation of the IPR channel, an important dynamic behavior which is seldom discussed in previous IPR models. In addition, we find that the gating of the IPR channel is most likely to be a biochemical process that
. Finally, we used the patch-clamp experimental data to validate that the IPR channel indeed breaks detailed balance and thus is a nonequilibrium system which