Towards a unified theory of calmodulin regulation (calmodulation) of voltage-gated calcium and sodium channels

Manu Ben-Johny; Ivy E. Dick; Lingjie Sang; Worawan B. Limpitikul; Po Wei Kang; Jacqueline Niu; Rahul Banerjee; Wanjun Yang; Jennifer S. Babich; John B. Issa; Shin Rong Lee; Ho Namkung; Jiangyu Li; Manning Zhang; Philemon S. Yang; Hojjat Bazzazi; Paul J. Adams; Rosy Joshi-Mukherjee; Daniel N. Yue; David T. Yue

doi:10.2174/1874467208666150507110359

Towards a unified theory of calmodulin regulation (calmodulation) of voltage-gated calcium and sodium channels

Manu Ben-Johny, Ivy E. Dick, Lingjie Sang, Worawan B. Limpitikul, Po Wei Kang, Jacqueline Niu, Rahul Banerjee, Wanjun Yang, Jennifer S. Babich, John B. Issa, Shin Rong Lee, Ho Namkung, Jiangyu Li, Manning Zhang, Philemon S. Yang, Hojjat Bazzazi, Paul J. Adams, Rosy Joshi-Mukherjee, Daniel N. Yue, David T. Yue

School of Medicine

Research output: Contribution to journal › Article › peer-review

30 Scopus citations

Abstract

Voltage-gated Na and Ca₂₊ channels represent two major ion channel families that enable myriad biological functions including the generation of action potentials and the coupling of electrical and chemical signaling in cells. Calmodulin regulation (calmodulation) of these ion channels comprises a vital feedback mechanism with distinct physiological implications. Though long-sought, a shared understanding of the channel families remained elusive for two decades as the functional manifestations and the structural underpinnings of this modulation often appeared to diverge. Here, we review recent advancements in the understanding of calmodulation of Ca₂₊ and Na channels that suggest a remarkable similarity in their regulatory scheme. This interrelation between the two channel families now paves the way towards a unified mechanistic framework to understand vital calmodulin-dependent feedback and offers shared principles to approach related channelopathic diseases. An exciting era of synergistic study now looms.

Original language	English (US)
Pages (from-to)	188-205
Number of pages	18
Journal	Current Molecular Pharmacology
Volume	8
Issue number	2
DOIs	https://doi.org/10.2174/1874467208666150507110359
State	Published - Oct 1 2015

Keywords

Calcium channels
Calmodulation
Sodium channels

ASJC Scopus subject areas

Molecular Medicine
Pharmacology
Drug Discovery

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10.2174/1874467208666150507110359

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Ben-Johny, M., Dick, I. E., Sang, L., Limpitikul, W. B., Kang, P. W., Niu, J., Banerjee, R., Yang, W., Babich, J. S., Issa, J. B., Lee, S. R., Namkung, H., Li, J., Zhang, M., Yang, P. S., Bazzazi, H., Adams, P. J., Joshi-Mukherjee, R., Yue, D. N., & Yue, D. T. (2015). Towards a unified theory of calmodulin regulation (calmodulation) of voltage-gated calcium and sodium channels. Current Molecular Pharmacology, 8(2), 188-205. https://doi.org/10.2174/1874467208666150507110359

Ben-Johny, M, Dick, IE, Sang, L, Limpitikul, WB, Kang, PW, Niu, J, Banerjee, R, Yang, W, Babich, JS, Issa, JB, Lee, SR, Namkung, H, Li, J, Zhang, M, Yang, PS, Bazzazi, H, Adams, PJ, Joshi-Mukherjee, R, Yue, DN & Yue, DT 2015, 'Towards a unified theory of calmodulin regulation (calmodulation) of voltage-gated calcium and sodium channels', Current Molecular Pharmacology, vol. 8, no. 2, pp. 188-205. https://doi.org/10.2174/1874467208666150507110359

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abstract = "Voltage-gated Na and Ca2+ channels represent two major ion channel families that enable myriad biological functions including the generation of action potentials and the coupling of electrical and chemical signaling in cells. Calmodulin regulation (calmodulation) of these ion channels comprises a vital feedback mechanism with distinct physiological implications. Though long-sought, a shared understanding of the channel families remained elusive for two decades as the functional manifestations and the structural underpinnings of this modulation often appeared to diverge. Here, we review recent advancements in the understanding of calmodulation of Ca2+ and Na channels that suggest a remarkable similarity in their regulatory scheme. This interrelation between the two channel families now paves the way towards a unified mechanistic framework to understand vital calmodulin-dependent feedback and offers shared principles to approach related channelopathic diseases. An exciting era of synergistic study now looms.",

keywords = "Calcium channels, Calmodulation, Sodium channels",

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AU - Limpitikul, Worawan B.

AU - Kang, Po Wei

AU - Niu, Jacqueline

AU - Banerjee, Rahul

AU - Yang, Wanjun

AU - Babich, Jennifer S.

AU - Issa, John B.

AU - Lee, Shin Rong

AU - Namkung, Ho

AU - Li, Jiangyu

AU - Zhang, Manning

AU - Yang, Philemon S.

AU - Bazzazi, Hojjat

AU - Adams, Paul J.

AU - Joshi-Mukherjee, Rosy

AU - Yue, Daniel N.

AU - Yue, David T.

PY - 2015/10/1

Y1 - 2015/10/1

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AB - Voltage-gated Na and Ca2+ channels represent two major ion channel families that enable myriad biological functions including the generation of action potentials and the coupling of electrical and chemical signaling in cells. Calmodulin regulation (calmodulation) of these ion channels comprises a vital feedback mechanism with distinct physiological implications. Though long-sought, a shared understanding of the channel families remained elusive for two decades as the functional manifestations and the structural underpinnings of this modulation often appeared to diverge. Here, we review recent advancements in the understanding of calmodulation of Ca2+ and Na channels that suggest a remarkable similarity in their regulatory scheme. This interrelation between the two channel families now paves the way towards a unified mechanistic framework to understand vital calmodulin-dependent feedback and offers shared principles to approach related channelopathic diseases. An exciting era of synergistic study now looms.

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Towards a unified theory of calmodulin regulation (calmodulation) of voltage-gated calcium and sodium channels

Abstract

Keywords

ASJC Scopus subject areas

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