期刊
PROGRESS IN NEUROBIOLOGY
卷 94, 期 2, 页码 115-132出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pneurobio.2011.04.009
关键词
Axonal targeting; Action potential; Neurotransmitter release; Voltage-gated potassium channel; Axon initial segment; Neuronal polarity
资金
- National Multiple Sclerosis Society [TA3012A1]
- National Institute of Neurological Disorders and Stroke/National Institutes of Health [R01NS062720]
Precise localization of various ion channels into proper subcellular compartments is crucial for neuronal excitability and synaptic transmission. Axonal K+ channels that are activated by depolarization of the membrane potential participate in the repolarizing phase of the action potential, and hence regulate action potential firing patterns, which encode output signals. Moreover, some of these channels can directly control neurotransmitter release at axonal terminals by constraining local membrane excitability and limiting Ca2+ influx. K+ channels differ not only in biophysical and pharmacological properties, but in expression and subcellular distribution as well. Importantly, proper targeting of channel proteins is a prerequisite for electrical and chemical functions of axons. In this review, we first highlight recent studies that demonstrate different roles of axonal K+ channels in the local regulation of axonal excitability. Next, we focus on research progress in identifying axonal targeting motifs and machinery of several different types of K+ channels present in axons. Regulation of K+ channel targeting and activity may underlie a novel form of neuronal plasticity. This research field can contribute to generating novel therapeutic strategies through manipulating neuronal excitability in treating neurological diseases, such as multiple sclerosis, neuropathic pain, and Alzheimer's disease. (C) 2011 Elsevier Ltd. All rights reserved.
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