Free-energy relationships in ion channels activated by voltage and ligand.
Free-energy relationships in ion channels activated by voltage and ligand.
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DOI：
10.1085/jgp.201210860
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发表时间：
2013-01
期刊：
影响因子：
--
通讯作者：
Chanda B
中科院分区：
文献类型：
--
作者：
Chowdhury S;Chanda B
Many ion channels are modulated by multiple stimuli, which allow them to integrate a variety of cellular signals and precisely respond to physiological needs. Understanding how these different signaling pathways interact has been a challenge in part because of the complexity of underlying models. In this study, we analyzed the energetic relationships in polymodal ion channels using linkage principles. We first show that in proteins dually modulated by voltage and ligand, the net free-energy change can be obtained by measuring the charge-voltage (Q-V) relationship in zero ligand condition and the ligand binding curve at highly depolarizing membrane voltages. Next, we show that the voltage-dependent changes in ligand occupancy of the protein can be directly obtained by measuring the Q-V curves at multiple ligand concentrations. When a single reference ligand binding curve is available, this relationship allows us to reconstruct ligand binding curves at different voltages. More significantly, we establish that the shift of the Q-V curve between zero and saturating ligand concentration is a direct estimate of the interaction energy between the ligand- and voltage-dependent pathway. These free-energy relationships were tested by numerical simulations of a detailed gating model of the BK channel. Furthermore, as a proof of principle, we estimate the interaction energy between the ligand binding and voltage-dependent pathways for HCN2 channels whose ligand binding curves at various voltages are available. These emerging principles will be useful for high-throughput mutagenesis studies aimed at identifying interaction pathways between various regulatory domains in a polymodal ion channel.
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影响因子：
16.2
作者：
Aggarwal, SK;MacKinnon, R
通讯作者：
MacKinnon, R
DOI：
10.1085/jgp.109.5.647
发表时间：
1997-05
期刊：
The Journal of general physiology
影响因子：
--
作者：
Cui J;Cox DH;Aldrich RW
通讯作者：
Aldrich RW
影响因子：
2.9
作者：
Cui, JM;Aldrich, RW
通讯作者：
Aldrich, RW
影响因子：
14.8
作者：
Kusch, Jana;Thon, Susanne;Benndorf, Klaus
通讯作者：
Benndorf, Klaus
影响因子：
64.8
作者：
DECOURSEY, TE;CHANDY, KG;CAHALAN, MD
通讯作者：
CAHALAN, MD