Dissection of voltage-gated sodium channels in developing cochlear sensory epithelia

Zhou, You; Fang, Fang-Hao; Liu, Zhi-Rui; Ji, Yonghua

doi:10.1007/s13238-015-0157-1

Cited by 2 publications

(6 citation statements)

References 16 publications

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“…Furthermore, three subtypes (Nav1.5a, 1.8a, and 1.9a) that mediate TTXinsensitive currents were also detected in premature IHCs and OHCs. These results are consistent with previous findings identifying the full-length mRNA encoding nine VGSC subtypes in developing cochlear sensory epithelia [18]. However, it seems that the three subtypes with extremely low abundance (Nav1.5a, 1.8a, and 1.9a) cannot functionally mediate the detectable TTX-insensitive currents in immature hair cells [8,17].…”

Section: Composition Of Vgsc Subunits In Pre-hearing Hair Cellssupporting

confidence: 93%

“…channel transcripts. In our previous work, Nav1.6a mRNA was shown to have higher expression levels than the other eight subtypes in developing sensory epithelia [18]; however, the single-cell qPCR data here showed that the mRNA expression level of Nav1.6a was markedly lower than that of Nav1.7a in single hair cells. These inconsistent results may be due to the different experimental material used.…”

Section: Composition Of Vgsc Subunits In Pre-hearing Hair Cellscontrasting

confidence: 74%

“…current in developing IHCs has been shown to be highly sensitive to TTX [8,17]. Our previous study revealed that all known subtypes of VGSCs are expressed in mouse cochlear sensory epithelia before the onset of hearing and that various VGSC splicing variants might be important to adapt to the unique physiological properties of the immature cochlea [18]. These results point to pivotal roles for VGSCs in regulating spontaneous activity in the developing cochlea.…”

Section: Introductionmentioning

confidence: 91%

“…cDNA encoding two a subunits of Nav1.7 variants (CbmNav1.7a and CbmNav1.7b) (GenBank Numbers: KM373695.1 and KM373696.1) cloned from the developing cochlear sensory epithelia in our previous work [18] and wild-type Nav1.7a from peripheral dorsal root ganglion (DRG) neurons (GenBank Number: NM-001290674.1) were synthesized and each cloned into the pIRES2 expression vector with an EGFP tag. To investigate the effects of different substitution/deletions of amino acid residues on channel properties which were induced by various posttranscriptional modification events, nine mutants (1-9) were generated and functionally compared.…”

Section: Plasmid Construction and Expressionmentioning

confidence: 99%

“…When compared to the typical wtNav1.7 variant from peripheral DRG neurons, CbmNav1.7a and CbmNav1.7b cloned from developing cochlear sensory epithelia have been characterized by distinct molecular structures produced by three alternative splicing and three RNA editing events [18] (Fig. 3A, B).…”

Section: Functional Characterization Of Nav17 Variants In Cochlear Sensory Epitheliamentioning

confidence: 99%

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Distribution and Functional Characteristics of Voltage-Gated Sodium Channels in Immature Cochlear Hair Cells

et al. 2019

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Voltage-gated sodium channels (VGSCs) are transiently expressed in cochlear hair cells before hearing onset and play an indispensable role in shaping spontaneous activity. In this study, we showed that Na ? currents shaped the spontaneous action potentials in developing mouse inner hair cells (IHCs) by decreasing the time required for the membrane potential to reach the actionpotential threshold. In immature IHCs, we identified 9 known VGSC subtypes (Nav1.1a-1.9a), among which Nav1.7a was the most highly expressed subtype and the main contributor to Na ? currents in developing hair cells. Electrophysiological recordings of two cochlea-specific Nav1.7 variants (CbmNav1.7a and CbmNav1.7b) revealed a novel loss-of-function mutation (C934R) at the extracellular linker between segments 5 and 6 of domain II. In addition, post-transcriptional modification events, such as alternative splicing and RNA editing, amended the gating properties and kinetic features of CbmNav1.7a (C934). These results provide molecular and functional characteristics of VGSCs in mammalian IHCs and their contributions to spontaneous physiological activity during cochlear maturation.

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Section: Composition Of Vgsc Subunits In Pre-hearing Hair Cellssupporting

confidence: 93%

Section: Composition Of Vgsc Subunits In Pre-hearing Hair Cellscontrasting

confidence: 74%

Section: Introductionmentioning

confidence: 91%

Section: Plasmid Construction and Expressionmentioning

confidence: 99%

Section: Functional Characterization Of Nav17 Variants In Cochlear Sensory Epitheliamentioning

confidence: 99%

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Distribution and Functional Characteristics of Voltage-Gated Sodium Channels in Immature Cochlear Hair Cells

et al. 2019

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Voltage-gated Sodium Channels in Sensory Information Processing

Zhou

Pan

Tan

et al. 2019

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Action potential is a form of electric signaling responsibly for conducting neural firing in organisms. Voltage-gated sodium channels (VGSCs) are key molecules dedicating to the initiation and propagation of action potentials, playing an indispensable role in processing excitable activity. The foundational sensory of human covering vision, auditory, olfactory, taste and tactile perceive the outer world rely on normal physiological function of VGSCs, which play as a root dancing in music of life. The aberrant genetics and endogenous regulation of VGSCs in most cases give rise to related clinical symptom such as hyperpselaphesia, parosphresia, and so on. This review highlights recent advances in the study of VGSCs in sensory systems which may facilitate the fresh understanding of VGSCs in sensory information processing and provide a novel pharmacological target for treatment of sensory system related clinical disease.

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Dissection of voltage-gated sodium channels in developing cochlear sensory epithelia

Cited by 2 publications

References 16 publications

Distribution and Functional Characteristics of Voltage-Gated Sodium Channels in Immature Cochlear Hair Cells

Distribution and Functional Characteristics of Voltage-Gated Sodium Channels in Immature Cochlear Hair Cells

Voltage-gated Sodium Channels in Sensory Information Processing

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