Modulation of muscle rNav1.4 Na+ channel isoform by arachidonic acid and its non-metabolized analog
✍ Scribed by Hua Gu; Yan-Jia Fang; Yan-Lin He; Ji Sun; Jian Zhu; Yan-Ai Mei
- Publisher
- John Wiley and Sons
- Year
- 2009
- Tongue
- English
- Weight
- 218 KB
- Volume
- 219
- Category
- Article
- ISSN
- 0021-9541
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✦ Synopsis
Abstract
Arachidonic acid (AA) and its metabolic products are important second messengers which exert many biological actions, including modulation of various ion channels. However, the blockage of muscle Na^+^ channel isoforms by AA has not been examined in detail. Here, we investigated the modulating effects of AA on muscle rNa~V~1.4 isoforms expressed in human embryonic kidney 293 cells. The results revealed that AA has both activation and inhibitory effects on rNa~V~1.4 currents depending on the depolarizing potential: AA increased the rNa~V~1.4 current evoked by a depolarization of −30 or −40 mV, but significantly decreased the rNa~V~1.4 current evoked by a depolarization of membrane potential over −10 mV. At concentrations of 1–500 µM, the inhibitory effect on the rNa~V~1.4 current induced by AA was dose‐dependent and reversible. In addition to modulating the amplitude of the rNa~V~1.4 current, AA significantly modulated the steady‐state activation and inactivation properties of rNa~V~1.4 channels. Furthermore, treatment with AA resulted in a fairly slow recovery of the rNa~V~1.4 channel from inactivation; however, the inhibitory effect of AA was not changed by repetitive pulses or by changing frequency. The effect of AA on rNa~V~1.4 currents was completely mimicked by ETYA, the non‐metabolized analog of AA. Our data demonstrated that AA, but not the metabolic products of AA, can voltage‐dependent modulate rNa~V~1.4 currents. J. Cell. Physiol. 219: 173–182, 2009. © 2008 Wiley‐Liss, Inc.