HCN channels are not required for mechanotransduction in sensory hair cells of the mouse inner ear.

The molecular composition of the hair cell transduction channel has not been identified. Here we explore the novel hypothesis that hair cell transduction channels include HCN subunits. The HCN family of ion channels includes four members, HCN1-4. They were originally identified as the molecular corr...

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Autores principales:	Geoffrey C Horwitz, Andrea Lelli, Gwenaëlle S G Géléoc, Jeffrey R Holt
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/00b12e0b98f94836a4f3dee1008149ee
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spelling	oai:doaj.org-article:00b12e0b98f94836a4f3dee1008149ee2021-11-25T06:26:53ZHCN channels are not required for mechanotransduction in sensory hair cells of the mouse inner ear.1932-620310.1371/journal.pone.0008627https://doaj.org/article/00b12e0b98f94836a4f3dee1008149ee2010-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20062532/?tool=EBIhttps://doaj.org/toc/1932-6203The molecular composition of the hair cell transduction channel has not been identified. Here we explore the novel hypothesis that hair cell transduction channels include HCN subunits. The HCN family of ion channels includes four members, HCN1-4. They were originally identified as the molecular correlates of the hyperpolarization-activated, cyclic nucleotide gated ion channels that carry currents known as If, IQ or Ih. However, based on recent evidence it has been suggested that HCN subunits may also be components of the elusive hair cell transduction channel. To investigate this hypothesis we examined expression of mRNA that encodes HCN1-4 in sensory epithelia of the mouse inner ear, immunolocalization of HCN subunits 1, 2 and 4, uptake of the transduction channel permeable dye, FM1-43 and electrophysiological measurement of mechanotransduction current. Dye uptake and transduction current were assayed in cochlear and vestibular hair cells of wildtype mice exposed to HCN channel blockers or a dominant-negative form of HCN2 that contained a pore mutation and in mutant mice that lacked HCN1, HCN2 or both. We found robust expression of HCNs 1, 2 and 4 but little evidence that localized HCN subunits in hair bundles, the site of mechanotransduction. Although high concentrations of the HCN antagonist, ZD7288, blocked 50-70% of the transduction current, we found no reduction of transduction current in either cochlear or vestibular hair cells of HCN1- or HCN2- deficient mice relative to wild-type mice. Furthermore, mice that lacked both HCN1 and HCN2 also had normal transduction currents. Lastly, we found that mice exposed to the dominant-negative mutant form of HCN2 had normal transduction currents as well. Taken together, the evidence suggests that HCN subunits are not required for mechanotransduction in hair cells of the mouse inner ear.Geoffrey C HorwitzAndrea LelliGwenaëlle S G GéléocJeffrey R HoltPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 1, p e8627 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Geoffrey C Horwitz Andrea Lelli Gwenaëlle S G Géléoc Jeffrey R Holt HCN channels are not required for mechanotransduction in sensory hair cells of the mouse inner ear.
description	The molecular composition of the hair cell transduction channel has not been identified. Here we explore the novel hypothesis that hair cell transduction channels include HCN subunits. The HCN family of ion channels includes four members, HCN1-4. They were originally identified as the molecular correlates of the hyperpolarization-activated, cyclic nucleotide gated ion channels that carry currents known as If, IQ or Ih. However, based on recent evidence it has been suggested that HCN subunits may also be components of the elusive hair cell transduction channel. To investigate this hypothesis we examined expression of mRNA that encodes HCN1-4 in sensory epithelia of the mouse inner ear, immunolocalization of HCN subunits 1, 2 and 4, uptake of the transduction channel permeable dye, FM1-43 and electrophysiological measurement of mechanotransduction current. Dye uptake and transduction current were assayed in cochlear and vestibular hair cells of wildtype mice exposed to HCN channel blockers or a dominant-negative form of HCN2 that contained a pore mutation and in mutant mice that lacked HCN1, HCN2 or both. We found robust expression of HCNs 1, 2 and 4 but little evidence that localized HCN subunits in hair bundles, the site of mechanotransduction. Although high concentrations of the HCN antagonist, ZD7288, blocked 50-70% of the transduction current, we found no reduction of transduction current in either cochlear or vestibular hair cells of HCN1- or HCN2- deficient mice relative to wild-type mice. Furthermore, mice that lacked both HCN1 and HCN2 also had normal transduction currents. Lastly, we found that mice exposed to the dominant-negative mutant form of HCN2 had normal transduction currents as well. Taken together, the evidence suggests that HCN subunits are not required for mechanotransduction in hair cells of the mouse inner ear.
format	article
author	Geoffrey C Horwitz Andrea Lelli Gwenaëlle S G Géléoc Jeffrey R Holt
author_facet	Geoffrey C Horwitz Andrea Lelli Gwenaëlle S G Géléoc Jeffrey R Holt
author_sort	Geoffrey C Horwitz
title	HCN channels are not required for mechanotransduction in sensory hair cells of the mouse inner ear.
title_short	HCN channels are not required for mechanotransduction in sensory hair cells of the mouse inner ear.
title_full	HCN channels are not required for mechanotransduction in sensory hair cells of the mouse inner ear.
title_fullStr	HCN channels are not required for mechanotransduction in sensory hair cells of the mouse inner ear.
title_full_unstemmed	HCN channels are not required for mechanotransduction in sensory hair cells of the mouse inner ear.
title_sort	hcn channels are not required for mechanotransduction in sensory hair cells of the mouse inner ear.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/00b12e0b98f94836a4f3dee1008149ee
work_keys_str_mv	AT geoffreychorwitz hcnchannelsarenotrequiredformechanotransductioninsensoryhaircellsofthemouseinnerear AT andrealelli hcnchannelsarenotrequiredformechanotransductioninsensoryhaircellsofthemouseinnerear AT gwenaellesggeleoc hcnchannelsarenotrequiredformechanotransductioninsensoryhaircellsofthemouseinnerear AT jeffreyrholt hcnchannelsarenotrequiredformechanotransductioninsensoryhaircellsofthemouseinnerear
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HCN channels are not required for mechanotransduction in sensory hair cells of the mouse inner ear.

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