Gentamicin Blocks the ACh-Induced BK Current in Guinea Pig Type II Vestibular Hair Cells by Competing with Ca2 at the l-Type Calcium ChannelReportar como inadecuado




Gentamicin Blocks the ACh-Induced BK Current in Guinea Pig Type II Vestibular Hair Cells by Competing with Ca2 at the l-Type Calcium Channel - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

1

Department of Otorhinolaryngology, Union Hospital of Tongji Medical College, Hua-Zhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China

2

Institute of Otorhinolaryngology, Union Hospital, Tongji Medical College, Hua-Zhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China

3

Key Laboratory of Neurological Disease, Ministry of Education, Tongji Medical College, Hua-Zhong University of Science and Technology, Wuhan 430022, China



These authors contributed equally to this work.





*

Author to whom correspondence should be addressed.



Abstract Type II vestibular hair cells VHCs II contain big-conductance Ca2+-dependent K+ channels BK and L-type calcium channels. Our previous studies in guinea pig VHCs II indicated that acetylcholine ACh evoked the BK current by triggering the influx of Ca2+ ions through l-type Ca2+ channels, which was mediated by M2 muscarinic ACh receptor mAChRs. Aminoglycoside antibiotics, such as gentamicin GM, are known to have vestibulotoxicity, including damaging effects on the efferent nerve endings on VHCs II. This study used the whole-cell patch clamp technique to determine whether GM affects the vestibular efferent system at postsynaptic M2-mAChRs or the membrane ion channels. We found that GM could block the ACh-induced BK current and that inhibition was reversible, voltage-independent, and dose-dependent with an IC50 value of 36.3 ± 7.8 µM. Increasing the ACh concentration had little influence on GM blocking effect, but increasing the extracellular Ca2+ concentration Ca2+o could antagonize it. Moreover, 50 µM GM potently blocked Ca2+ currents activated by -Bay-K8644, but did not block BK currents induced by NS1619. These observations indicate that GM most likely blocks the M2 mAChR-mediated response by competing with Ca2+ at the l-type calcium channel. These results provide insights into the vestibulotoxicity of aminoglycoside antibiotics on mammalian VHCs II. View Full-Text

Keywords: gentamicin; vestibular hair cells; big conductance calcium-dependent potassium channel; acetylcholine; calcium channel gentamicin; vestibular hair cells; big conductance calcium-dependent potassium channel; acetylcholine; calcium channel





Autor: Hong Yu 1,†, Chang-Kai Guo 1,†, Yi Wang 1, Tao Zhou 1 and Wei-Jia Kong 1,2,3,*

Fuente: http://mdpi.com/



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