English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Cardiac pacemaker function of HCN4 channels in mice is confined to embryonic development and requires cyclic AMP

Harzheim, D., Pfeiffer, K. H., Fabritz, L., Kremmer, E., Buch, T., Waisman, A., et al. (2008). Cardiac pacemaker function of HCN4 channels in mice is confined to embryonic development and requires cyclic AMP. EMBO Journal, 27(4), 692-703.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0028-6491-8 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0028-6492-6
Genre: Journal Article

Files

show Files
hide Files
:
Harzheim_Cardiac.pdf (Any fulltext), 2MB
 
File Permalink:
-
Name:
Harzheim_Cardiac.pdf
Description:
-
Visibility:
Private
MIME-Type / Checksum:
application/pdf
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-

Locators

show

Creators

show
hide
 Creators:
Harzheim, D.1, Author
Pfeiffer, K. H., Author
Fabritz, L., Author
Kremmer, E., Author
Buch, T., Author
Waisman, A., Author
Kirchhof, P., Author
Kaupp, U. B.1, Author
Seifert, R.1, Author
Affiliations:
1External Organizations, ou_persistent22              

Content

show
hide
Free keywords: -
 Abstract: Important targets for cAMP signalling in the heart are hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels that underlie the depolarizing 'pacemaker' current, If. We studied the role of If in mice, in which binding of cAMP to HCN4 channels was abolished by a single amino-acid exchange (R669Q). Homozygous HCN4(R669Q/R669Q) mice die during embryonic development. Prior to E12, homozygous and heterozygous embryos display reduced heart rates and show no or attenuated responses to catecholaminergic stimulation. Adult heterozygous mice display normal heart rates at rest and during exercise. However, following beta-adrenergic stimulation, hearts exhibit pauses and sino-atrial node block. Our results demonstrate that in the embryo, HCN4 is a true cardiac pacemaker and elevation of HCN4 channel activity by cAMP is essential for viability. In adult mice, an important function of HCN4 channels is to prevent sinus pauses during and after stress while their role as a pacemaker of the murine heart is put into question. Most importantly, our results indicate that HCN4 channels can fulfil their physiological function only when cAMP is bound

Details

show
hide
Language(s):
 Dates: 2008
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: ISI: ISI:000253409300010
ISSN: 0261-4189
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: EMBO Journal
  Alternative Title : EMBO J.
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 27 (4) Sequence Number: - Start / End Page: 692 - 703 Identifier: -