Document Detail

HCN3 Contributes to the Ventricular Action Potential Waveform in the Murine Heart.
MedLine Citation:
PMID:  21903939     Owner:  NLM     Status:  Publisher    
Rationale:The hyperpolarization-activated current I(h) that is generated by hyperpolarization-activated cyclic nucleotide-gated channels (HCNs) plays a key role in the control of pacemaker activity in sinoatrial node cells of the heart. By contrast, it is unclear whether I(h) is also relevant for normal function of cardiac ventricles.Objective:To study the role of the HCN3-mediated component of ventricular I(h) in normal ventricular function.Methods and Results:To test the hypothesis that HCN3 regulates the ventricular action potential waveform, we have generated and analyzed a HCN3-deficient mouse line. At basal heart rate, mice deficient for HCN3 displayed a profound increase in the T-wave amplitude in telemetric electrocardiographic measurements. Action potential recordings on isolated ventricular myocytes indicate that this effect was caused by an acceleration of the late repolarization phase in epicardial myocytes. Furthermore, the resting membrane potential was shifted to more hyperpolarized potentials in HCN3-deficient mice. Cardiomyocytes of HCN3-deficient mice displayed approximately 30% reduction of total I(h). At physiological ionic conditions, the HCN3-mediated current had a reversal potential of approximately -35 mV and displayed ultraslow deactivation kinetics.Conclusions:We propose that HCN3 together with other members of the HCN channel family confer a depolarizing background current that regulates ventricular resting potential and counteracts the action of hyperpolarizing potassium currents in late repolarization. In conclusion, our data indicate that HCN3 plays an important role in shaping the cardiac action potential waveform.
Stefanie Fenske; Robert Mader; Andreas Scharr; Christos Paparizos; Xiaochun Cao-Ehlker; Stylianos Michalakis; Lior Shaltiel; Martha Weidinger; Juliane Stieber; Susanne Feil; Robert Feil; Franz Hofmann; Christian Wahl-Schott; Martin Biel
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-9-8
Journal Detail:
Title:  Circulation research     Volume:  -     ISSN:  1524-4571     ISO Abbreviation:  -     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-9-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0047103     Medline TA:  Circ Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Center for Integrated Protein Science CIPS-M and Zentrum für Pharmaforschung, Department Pharmazie, Ludwig-Maximilians-Universität München, München, Germany; Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Friedrich-Alexander-Universität Erlangen-Nürnbe, Erlangen, Germany; Interfakultäres Institut für Biochemie, Universität Tübingen, Tübingen, Germany; Institut für Pharmakologie und Toxikologie der Technischen Universität München, München, Germany.
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