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: Sodium channels, calcium channels, calmodulation.
Current Molecular Pharmacology
Title:Towards a Unified Theory of Calmodulin Regulation (Calmodulation) of Voltage-Gated Calcium and Sodium Channels
Volume: 8
Author(s): Shin Rong Lee, David T. Yue, Daniel N. Yue, Rosy Joshi-Mukherjee, Paul J. Adams, Hojjat Bazzazi, Philemon S. Yang, Manning Zhang, Jiangyu Li, Ho Namkung, Manu Ben-Johny, John B. Issa, Jennifer S. Babich, Wanjun Yang, Rahul Banerjee, Jacqueline Niu, Po Wei Kang, Worawan B. Limpitikul, Lingjie Sang and Ivy E. Dick
Affiliation:
Keywords: Sodium channels, calcium channels, calmodulation.
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.
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Cite this article as:
Rong Lee Shin, T. Yue David, N. Yue Daniel, Joshi-Mukherjee Rosy, J. Adams Paul, Bazzazi Hojjat, S. Yang Philemon, Zhang Manning, Li Jiangyu, Namkung Ho, Ben-Johny Manu, B. Issa John, S. Babich Jennifer, Yang Wanjun, Banerjee Rahul, Niu Jacqueline, Wei Kang Po, B. Limpitikul Worawan, Sang Lingjie and E. Dick Ivy, Towards a Unified Theory of Calmodulin Regulation (Calmodulation) of Voltage-Gated Calcium and Sodium Channels, Current Molecular Pharmacology 2015; 8 (2) . https://dx.doi.org/10.2174/1874467208666150507110359
DOI https://dx.doi.org/10.2174/1874467208666150507110359 |
Print ISSN 1874-4672 |
Publisher Name Bentham Science Publisher |
Online ISSN 1874-4702 |
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