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 and David T. Yue Pages 188 - 205 ( 18 )
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.
Sodium channels, calcium channels, calmodulation.
Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Ross Building, Room 713, 720 Rutland Avenue, Baltimore, MD 21205, USA.