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Nitric oxide selectively suppresses IH currents mediated by HCN1 containing channels

journal contribution
posted on 17.10.2014, 12:52 by Cornelia Kopp-Scheinpflug, Beatrice M. Pigott, Ian D. Forsythe
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.

History

Citation

The Journal of Physiology, 2014. Accepted.

Author affiliation

/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Biological Sciences/Department of Cell Physiology and Pharmacology

Version

AM (Accepted Manuscript)

Published in

The Journal of Physiology

Publisher

Wiley

issn

0022-3751

eissn

1469-7793

Copyright date

2014

Available date

21/01/2016

Publisher version

http://onlinelibrary.wiley.com/doi/10.1113/jphysiol.2014.282194/abstract

Notes

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.

Language

en

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