AJP - Regu AJP: Endocrinology and Metabolism
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Regul Integr Comp Physiol 297: R412-R420, 2009. First published June 10, 2009; doi:10.1152/ajpregu.00036.2009
0363-6119/09 $8.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
297/2/R412    most recent
00036.2009v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Google Scholar
Right arrow Articles by Steele, S. L.
Right arrow Articles by Perry, S. F.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Steele, S. L.
Right arrow Articles by Perry, S. F.

ARTICLES

Loss of M2 muscarinic receptor function inhibits development of hypoxic bradycardia and alters cardiac β-adrenergic sensitivity in larval zebrafish (Danio rerio)

Shelby L. Steele,1 Kwok Hong Andy Lo,2 Vincent Wai Tsun Li,2 Shuk Han Cheng,2 Marc Ekker,1 and Steve F. Perry1

1Department of Biology, University of Ottawa, Ottawa, Ontario, Canada; and 2Department of Biology and Chemistry, City University of Hong Kong, Kowloon, Hong Kong

Submitted 21 January 2009 ; accepted in final form 2 June 2009

Fish exposed to hypoxia develop decreased heart rate, or bradycardia, the physiological significance of which remains unknown. The general muscarinic receptor antagonist atropine abolishes the development of this hypoxic bradycardia, suggesting the involvement of muscarinic receptors. In this study, we tested the hypothesis that the hypoxic bradycardia is mediated specifically by stimulation of the M2 muscarinic receptor, the most abundant subtype in the vertebrate heart. Zebrafish (Danio rerio) were reared at two levels of hypoxia (30 and 40 Torr PO2) from the point of fertilization. In hypoxic fish, the heart rate was significantly lower than in normoxic controls from 2 to 10 days postfertilization (dpf). At the more severe level of hypoxia (30 Torr PO2), there were significant increases in the relative mRNA expression of M2 and the cardiac type β-adrenergic receptors (β1AR, β2aAR, and β2bAR) at 4 dpf. The hypoxic bradycardia was abolished (at 40 Torr PO2) or significantly attenuated (at 30 Torr PO2) in larvae experiencing M2 receptor knockdown (using morpholino antisense oligonucleotides). Sham-injected larvae exhibited typical hypoxic bradycardia in both hypoxic regimens. The expression of β1AR, β2aAR, β2bAR, and M2 mRNA was altered at various stages between 1 and 4 dpf in larvae experiencing M2 receptor knockdown. Interestingly, M2 receptor knockdown revealed a cardioinhibitory role for the β2-adrenergic receptor. This is the first study to demonstrate a specific role of the M2 muscarinic receptor in the initiation of hypoxic bradycardia in fish.

heart rate; cardiovascular function; morpholino; knockdown


Address for reprint requests and other correspondence: S. F. Perry, Univ. of Ottawa, Dept. of Biology, Ottawa, ON, Canada K1N 6N5 (e-mail: sfperry{at}uottawa.ca)






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2009 by the American Physiological Society.