Deutsch
 
Hilfe Datenschutzhinweis Impressum
  DetailsucheBrowse

Datensatz

DATENSATZ AKTIONENEXPORT
  cAMP sensitivity of HCN pacemaker channels determines basal heart rate but is not critical for autonomic rate control

Schweizer, P. A., Duhme, N., Thomas, D., Becker, R., Zehelein, J., Draguhn, A., et al. (2010). cAMP sensitivity of HCN pacemaker channels determines basal heart rate but is not critical for autonomic rate control. Circulation: Arrhythmia and Electrophysiology, 3(5), 542-552. doi:10.1161/CIRCEP.110.949768.

Item is

Basisdaten

einblenden: ausblenden:
Genre: Zeitschriftenartikel
Alternativer Titel : cAMP sensitivity of HCN pacemaker channels determines basal heart rate but is not critical for autonomic rate control

Dateien

einblenden: Dateien
ausblenden: Dateien
:
CirculArrhythmElectrophysiol_3_2010_542.pdf (beliebiger Volltext), 845KB
 
Datei-Permalink:
-
Name:
CirculArrhythmElectrophysiol_3_2010_542.pdf
Beschreibung:
-
OA-Status:
Sichtbarkeit:
Eingeschränkt (Max Planck Institute for Medical Research, MHMF; )
MIME-Typ / Prüfsumme:
application/pdf
Technische Metadaten:
Copyright Datum:
-
Copyright Info:
-
Lizenz:
-

Externe Referenzen

einblenden:
ausblenden:
Beschreibung:
-
OA-Status:
externe Referenz:
https://doi.org/10.1161/CIRCEP.110.949768 (beliebiger Volltext)
Beschreibung:
-
OA-Status:

Urheber

einblenden:
ausblenden:
 Urheber:
Schweizer, Patrick A., Autor
Duhme, Nana, Autor
Thomas, Dierck, Autor
Becker, Rüdiger, Autor
Zehelein, Joerg1, Autor           
Draguhn, Andreas2, Autor           
Bruehl, Claus, Autor
Katus, Hugo A., Autor
Koenen, Michael1, Autor           
Affiliations:
1Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Max Planck Society, ou_1497704              
2Department of Cell Physiology, Max Planck Institute for Medical Research, Max Planck Society, ou_1497701              

Inhalt

einblenden:
ausblenden:
Schlagwörter: Sinoatrial node, pacemaker, heart rate, ion channels, electrophysiology, HCN channels
 Zusammenfassung: BACKGROUND: HCN channels activate the pacemaker current I(f), which is thought to contribute significantly to generation and regulation of heart rhythm. HCN4 represents the dominant isotype in the sinoatrial node and binding of cAMP was suggested to be necessary for autonomic heart rate regulation. METHODS AND RESULTS: In a candidate gene approach, a heterozygous insertion of 13 nucleotides in exon 6 of the HCN4 gene leading to a truncated cyclic nucleotide-binding domain was identified in a 45-year-old woman with sinus bradycardia. Biophysical properties determined by whole-cell patch-clamp recording of HEK293 cells demonstrated that mutant subunits (HCN4-695X) were insensitive to cAMP. Heteromeric channels composed of wild-type and mutant subunits failed to respond to cAMP-like homomeric mutant channels, indicating a dominant-negative suppression of cAMP-induced channel activation by mutant subunits. Pedigree analysis identified 7 additional living carriers showing similar clinical phenotypes, that is, sinus node dysfunction with mean resting heart rate of 45.9±4.6 bpm (n=8) compared with 66.5±9.1 bpm of unaffected relatives (n=6; P<0.01). Clinical evaluation revealed no ischemic or structural heart disease in any family member. Importantly, mutant carriers exhibited normal heart rate variance and full ability to accelerate heart rate under physical activity or pharmacological stimulation. Moreover, mutant carriers displayed distinctive sinus arrhythmias and premature beats linked to adrenergic stress. CONCLUSIONS: In humans, cAMP responsiveness of I(f) determines basal heart rate but is not critical for maximum heart rate, heart rate variability, or chronotropic competence. Furthermore, cAMP-activated I(f) may stabilize heart rhythm during chronotropic response.

Details

einblenden:
ausblenden:
Sprache(n): eng - English
 Datum: 2010-03-012010-07-152010-08-072010-10-20
 Publikationsstatus: Erschienen
 Seiten: 12
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: Expertenbegutachtung
 Identifikatoren: eDoc: 664570
DOI: 10.1161/CIRCEP.110.949768
URI: http://www.ncbi.nlm.nih.gov/pubmed/20693575
Anderer: 7600
 Art des Abschluß: -

Veranstaltung

einblenden:

Entscheidung

einblenden:

Projektinformation

einblenden:

Quelle 1

einblenden:
ausblenden:
Titel: Circulation: Arrhythmia and Electrophysiology
  Alternativer Titel : Circulation: Arrhythmia and Electrophysiology
Genre der Quelle: Zeitschrift
 Urheber:
Affiliations:
Ort, Verlag, Ausgabe: Philadelphia, Pa. : Lippincott, Williams & Wilkins
Seiten: - Band / Heft: 3 (5) Artikelnummer: - Start- / Endseite: 542 - 552 Identifikator: ISSN: 1941-3149