期刊
NEUROSCIENCE
卷 114, 期 3, 页码 745-753出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/S0306-4522(02)00242-7
关键词
voltage-gated sodium channel; Chinese hamster ovary cell; voltage clamp; pain
Voltage-gated sodium channels consist of a pore-forming a subunit and two auxiliary beta subunits. Excitable cells express multiple alpha subtypes, designated Na(v)1.1-Na(v)1.9, and three beta subunits, designated beta1, beta2 and beta3. Understanding how the different a, subtypes, in combination with the various beta subunits, determine sodium channel behavior is important for elucidating the molecular basis of sodium channel functional diversity. In this study, we used whole-cell electrophysiological recording to examine the properties of the human Na(v)1.3 alpha subtype, stably expressed in Chinese hamster ovary cells, and to investigate modulation of Na(v)1.3 function by beta1, beta2 and beta3 subunits. In the absence of beta subunits, human Na(v)1.3 formed channels that inactivated rapidly (tau(inactivation) approximate to 0. 5 ms at 0 mV) and almost completely by the end of 190-ms-long depolarizations. Using an intracellular solution with aspartate as the main anion, the midpoint for channel activation was similar to -12 mV. The midpoint for inactivation, determined using 100-ms conditioning pulses, was similar to -47 mV. The time constant for reprinting of inactivated channels at -80 mV was similar to6 ms. Coexpression of beta1 or beta3 did not affect inactivation time course or the voltage dependence of activation, but shifted the inactivation curve similar to10 mV negative, and slowed the repriming rate ca. three-fold. 2 did not affect channel properties, either by itself or in combination with betaI or beta3. Na(v)1.3 expression is increased in damaged nociceptive peripheral afferents. This change in channel expression levels is correlated with the emergence of a rapidly inactivating and rapidly repriming sodium current, which has been proposed to contribute to the pathophysiology of neuropathic pain. The results of this study support the hypothesis that Na(v)1.3 may mediate this fast sodium current. (C) 2002 IBRO. Published by Elsevier Science Ltd. All rights reserved.
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