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Modulation by Clamping: Kv4 and KChIP Interactions

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Abstract

The rapidly inactivating (A-type) potassium channels regulate membrane excitability that defines the fundamental mechanism of neuronal functions such as pain signaling. Cytosolic Kv channel-interacting proteins KChIPs that belong to neuronal calcium sensor (NCS) family of calcium binding EF-hand proteins co-assemble with Kv4 (Shal) α subunits to form a native complex that encodes major components of neuronal somatodendritic A-type K+ current, ISA, in neurons and transient outward current, ITO, in cardiac myocytes. The specific binding of auxiliary KChIPs to the Kv4 N-terminus results in modulation of gating properties, surface expression and subunit assembly of Kv4 channels. Here, I attempt to emphasize the interaction between KChIPs and Kv4 based on recent progress made in understanding the structure complex in which a single KChIP1 molecule laterally clamps two neighboring Kv4.3 N-termini in a 4:4 manner. Greater insights into molecular mechanism between KChIPs and Kv4 interaction may provide therapeutic potentials of designing compounds aimed at disrupting the protein–protein interaction for treatment of membrane excitability-related disorders.

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Fig. 1
Fig. 2

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Abbreviations

KChIPs:

Kv channel-interacting proteins

NCS:

Neuronal calcium sensor

Kv:

Voltage-gated potassium channels

T1 domain:

Tetramerization domain

DREAM:

Downstream regulatory element antagonist modulator

Kv4.3N:

Kv4.3 N-terminus

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Acknowledgments

I would like to thank the lab members for their contributions to the work and Mr. Ping Liang for assistance in Figure 1. I am also very grateful to Dr Mike Stein for his comments on the manuscript. The preparation of this manuscript was supported by research grants from the National Science Foundation of China, 30630017 and the Ministry of Science Technology of China, 2006AA02Z183 and 2007CB512100 to KWW.

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Authors and Affiliations

  1. Neuroscience Research Institute and Department of Neurobiology, Key Laboratory for Neuroscience of the Ministry of Education, Center for Protein Sciences, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100083, China

    KeWei Wang

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  1. KeWei Wang
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Correspondence to KeWei Wang.

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Special issue article in honor of Dr. Ji-Sheng Han.

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Wang, K. Modulation by Clamping: Kv4 and KChIP Interactions. Neurochem Res 33, 1964–1969 (2008). https://doi.org/10.1007/s11064-008-9705-x

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  • DOI: https://doi.org/10.1007/s11064-008-9705-x

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