Document Detail

Characterization of HCN and cardiac function in a colonial ascidian.
MedLine Citation:
PMID:  21770038     Owner:  NLM     Status:  MEDLINE    
Hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels generate the rhythmic beating of mammalian hearts. We identified an HCN homolog in the colonial ascidian Botryllus schlosseri, a nonvertebrate chordate which possesses a tubular heart that beats bidirectionally. Contractions initiate at one end of the heart and travel across the length of the organ, and these periodically reverse, suggesting the presence of two pacemakers, one on each side. We find that HCN expression is highly enriched in cells scattered throughout the myocardium. We functionally analyzed the role of HCN channels in heartbeat using the antagonists Cilobradine and Zatebradine, which decreased the heartbeat in a reversible manner. We also assessed the role of β-adrenoreceptors in regulating HCN function using the antagonist Metoprolol, which lowered heartbeat rate (HR), as well as the agonist Isoproterenol, which did not alter HR, but caused simultaneous beating, analogous to a fibrillation. Measurements of direction and velocity of blood flow by making use of a novel system to study heart function in model systems amenable to live imaging revealed a significant correlation between heartbeat arrhythmia and drug treatment, similar to that observed with the same drugs in vertebrates. These results suggest that the heart pacemaker in tunicates may be homologous to that in their vertebrate counterparts in both development and function.
Annette Hellbach; Stefano Tiozzo; Jungho Ohn; Michael Liebling; Anthony W De Tomaso
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-07-18
Journal Detail:
Title:  Journal of experimental zoology. Part A, Ecological genetics and physiology     Volume:  315     ISSN:  1932-5231     ISO Abbreviation:  J Exp Zool A Ecol Genet Physiol     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-09-09     Completed Date:  2012-01-05     Revised Date:  2014-11-05    
Medline Journal Info:
Nlm Unique ID:  101297745     Medline TA:  J Exp Zool A Ecol Genet Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  476-86     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Wiley-Liss, Inc., A Wiley Company.
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MeSH Terms
Adrenergic beta-Antagonists / pharmacology
Benzazepines / pharmacology
Biological Clocks / physiology
Blood Flow Velocity / drug effects,  physiology
Cyclic Nucleotide-Gated Cation Channels / antagonists & inhibitors,  physiology*
Gene Expression Regulation, Developmental
Heart / physiology*
Metoprolol / pharmacology
Piperidines / pharmacology
RNA / analysis
Receptors, Adrenergic, beta / metabolism
Sequence Homology, Amino Acid
Urochordata / physiology*
Grant Support
R01 AG037966/AG/NIA NIH HHS; R01A104588//PHS HHS; R01DK405762/DK/NIDDK NIH HHS
Reg. No./Substance:
0/Adrenergic beta-Antagonists; 0/Benzazepines; 0/Cyclic Nucleotide-Gated Cation Channels; 0/Piperidines; 0/Receptors, Adrenergic, beta; 5O1LL04GJ3/cilobradine; 63231-63-0/RNA; GEB06NHM23/Metoprolol; TV27RY5876/zatebradine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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