期刊
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
卷 22, 期 2, 页码 145-152出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.semcdb.2010.10.004
关键词
Proteomics; Protein identification; Native ion channel protein complexes; Kv4 alpha subunits; Kv accessory subunits; Post-translational modifications; Quantitative mass spectrometry
资金
- National Institute of Health [R01-HL034161, R21-NS065295]
- National Center for Research Resources [NIH P41 RR000954, UL1 RR024992]
- NIH Neuroscience Blueprint Center Core [P30-NS057105]
- Agence Nationale de la Recherche [ANR-08-GENO-006]
- European Commission [NavEx-256397]
Voltage-gated K+ (Kv) channels are key determinants of membrane excitability in the nervous and cardiovascular systems, functioning to control resting membrane potentials, shape action potential waveforms and influence the responses to neurotransmitters and neurohormones. Consistent with this functional diversity, multiple types of Kv currents, with distinct biophysical properties and cellular/subcellular distributions, have been identified. Rapidly activating and inactivating Kv currents, typically referred to as I-A (A-type) in neurons, for example, regulate repetitive firing rates, action potential back-propagation (into dendrites) and modulate synaptic responses. Currents with similar properties, referred to as I-to,I-f (fast transient outward), expressed in cardiomyocytes, control the early phase of myocardial action potential repolarization. A number of studies have demonstrated critical roles for pore-forming (alpha) subunits of the Kv4 subfamily in the generation of native neuronal I-A and cardiac I-to,I-f channels. Studies in heterologous cells have also suggested important roles for a number of Kv channel accessory and regulatory proteins in the generation of functional I-A and I-to,I-f channels. Quantitative mass spectrometry-based proteomic analysis is increasingly recognized as a rapid and, importantly, unbiased, approach to identify the components of native macromolecular protein complexes. The recent application of proteomic approaches to identify the components of native neuronal (and cardiac) Kv4 channel complexes has revealed even greater complexity than anticipated. The continued emphasis on development of improved biochemical and analytical proteomic methods seems certain to accelerate progress and to provide important new insights into the molecular determinants of native ion channel protein complexes. (C) 2010 Elsevier Ltd. All rights reserved.
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