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Title of Journal: Pflugers Arch Eur J Physiol

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Abbravation: Pflügers Archiv - European Journal of Physiology

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Springer-Verlag

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10.1016/0165-1161(90)90059-w

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1432-2013

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Regulation of voltagegated sodium current by endo

Authors: Shuang Feng Melissa Pflueger ShuangXiu Lin Bradley R Groveman Jiping Su XianMin Yu
Publish Date: 2012/02/02
Volume: 463, Issue: 4, Pages: 571-584
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Abstract

Voltagegated sodium Na+ and potassium K+ channels have been found to be regulated by Src family kinases SFKs However how these channels are regulated by SFKs in cochlear spiral ganglion neurons SGNs remains unknown Here we report that altering the activity of endogenous SFKs modulated voltagegated Na+ but not K+ currents recorded in embryonic SGNs in culture Voltagegated Na+ current was suppressed by inhibition of endogenous SFKs or just Src and potentiated by the activation of these enzymes Detailed investigations showed that under basal conditions SFK inhibitor application did not significantly affect the voltagedependent activation but shifted the steadystate inactivation curves of Na+ currents and delayed the recovery of Na+ currents from inactivation Application of Src specific inhibitor Src40–58 not only shifted the inactivation curve but also delayed the recovery of Na+ currents and moved the voltagedependent activation curve towards the left The preinhibition of SFKs occluded all the effects induced by Src40–58 application except the left shift of the activation curve The activation of SFKs did not change either steadystate inactivation or recovery of Na+ currents but caused the left shift of the activation curve SFK inhibitor application effectively prevented all the effects induced by SFK activation suggesting that both the voltagedependent activation and steadystate inactivation of Na+ current are subjects of SFK regulation The different effects induced by activation versus inhibition of SFKs implied that under basal conditions endogenously active and inactive SFKs might be differentially involved in the regulation of voltagegated Na+ channels in SGNsSF is supported by the State Scholarship Fund of China 2009845013 This work was supported by a grant from NIH 5R01 NS05356704 to XMY We would like to thank Dr M W Salter for kindly supplying us Src inhibitory peptide Src40–58 SFK activator peptide EPQpYEEIPIA and control peptide EPQYEEIPIA We would also like to thank Drs M W Salter M Hildebrand and G Pitcher for the very constructive discussions

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