Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/29167
Title: Nitric oxide selectively suppresses IH currents mediated by HCN1 containing channels
Authors: Kopp-Scheinpflug, Cornelia
Pigott, Beatrice M.
Forsythe, Ian D.
First Published: 2014
Publisher: Wiley
Citation: The Journal of Physiology, 2014. Accepted.
Abstract: Hyperpolarization-activated non-specific cation permeable channels (HCN) mediate IH currents which are modulated by cGMP, cAMP and by nitric oxide (NO) signalling. Channel properties depend upon subunit composition (HCN1-4 and accessory subunits) as demonstrated in expression systems, however physiological relevance requires investigation in native neurons with intact intracellular signalling. Here we use the superior olivary complex (SOC), which exhibits a distinctive pattern of HCN1 and HCN2 expression, to investigate NO modulation of the respective IH currents, and compare properties in wild type and HCN1 knockout mice. The medial nucleus of the trapezoid body (MNTB) expresses HCN2 subunits exclusively, and sends inhibitory projections to the medial and lateral superior olives (MSO, LSO) and the superior paraolivary nucleus (SPN). In contrast to the MNTB, these target nuclei possess an IH with fast kinetics, and express HCN1 subunits. NO is generated in the SOC following synaptic activity and here we show that NO selectively suppresses HCN1, while enhancing IH mediated by HCN2 subunits. NO hyperpolarizes the half-activation of HCN1-mediated currents and slows the kinetics of native IH currents in the MSO, LSO and SPN. This modulation was independent of cGMP and absent in transgenic mice lacking HCN1. Independently, NO signalling depolarized the half-activation of HCN2-mediated IH currents in a cGMP-dependent manner. Thus NO selectively suppresses fast HCN1-mediated IH and facilitates a slow HCN2-mediated IH, so generating a spectrum of modulation, dependent on the local expression of HCN1 and/or HCN2 and the actions of NO signalling.
DOI Link: 10.1113/jphysiol.2014.282194
ISSN: 0022-3751
eISSN: 1469-7793
Links: http://onlinelibrary.wiley.com/doi/10.1113/jphysiol.2014.282194/abstract
http://hdl.handle.net/2381/29167
Version: Post-print
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © 2014, Wiley. Deposited with reference to the publisher’s archiving policy available on the SHERPA/RoMEO website. This is the peer reviewed version of the following 'Accepted Article'; doi: 10.1113/jphysiol.2014.282194., which has been published at http://onlinelibrary.wiley.com/doi/10.1113/jphysiol.2014.282194/abstract. This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving.
Description: The file associated with this record is embargoed until 12 months after the date of publication. The final published version may be available through the links above.
Appears in Collections:Published Articles, Dept. of Cell Physiology and Pharmacology

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IH_NO_MS CombinedFile_180814.pdfPre-review (submitted draft)2.36 MBAdobe PDFView/Open
JPHYSIOL-2014-282194v3-Forsythe.pdfPost-print7.94 MBAdobe PDFView/Open


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