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Title: Nitric oxide selectively suppresses IH currents mediated by HCN1 containing channels
Authors: Kopp-Scheinpflug, C.
Pigott, Beatrice M.
Forsythe, Ian D.
First Published: 17-Feb-2015
Publisher: Wiley, The Physiological Society
Citation: The Journal of Physiology
Abstract: Hyperpolarization-activated non-specific cation-permeable channels (HCN) mediate I[subscript: H] currents, which are modulated by cGMP and cAMP and by nitric oxide (NO) signalling. Channel properties depend upon subunit composition (HCN1–4 and accessory subunits) as demonstrated in expression systems, but 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 I[subscript: H] 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 I[subscript: H] with fast kinetics, and they express HCN1 subunits. NO is generated in the SOC following synaptic activity and here we show that NO selectively suppresses HCN1, while enhancing I[subscript: H] mediated by HCN2 subunits. NO hyperpolarizes the half-activation of HCN1-mediated currents and slows the kinetics of native I[subscript: H] currents in the MSO, LSO and SPN. This modulation was independent of cGMP and absent in transgenic mice lacking HCN1. Independently, NO signalling depolarizes the half-activation of HCN2-mediated I[subscript: H] currents in a cGMP-dependent manner. Thus, NO selectively suppresses fast HCN1-mediated I[subscript: H] and facilitates a slow HCN2-mediated I[subscript: H], so generating a spectrum of modulation, dependent on the local expression of HCN1 and/or HCN2.
DOI Link: 10.1113/jphysiol.2014.282194
ISSN: 0022-3751
eISSN: 1469-7793
Version: Post-print
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.
Appears in Collections:Published Articles, Dept. of Cell Physiology and Pharmacology

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