Loss of M^sub 2^ muscarinic receptor function inhibits development of hypoxic bradycardia and alters cardiac [beta]-adrenergic sensitivity in larval zebrafish (Danio rerio)

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology Vol. 297; no. 2; p. R412
• Main Authors: Steele, Shelby L, Lo, Kwok Hong Andy, Li, Vincent Wai Tsun, Cheng, Shuk Han, Ekker, Marc, Perry, Steve F
• Format: Journal Article
• Language: English
• Published: Bethesda American Physiological Society 01.08.2009
• Subjects: Cardiac arrhythmia; Gene expression; Heart rate; Hypoxia; Ribonucleic acid; RNA; Studies; Zebrafish
• ISSN: 0363-6119; 1522-1490

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 M... muscarinic receptor, the most abundant subtype in the vertebrate heart. Zebrafish (Danio rerio) were reared at two levels of hypoxia (30 and 40 Torr P...) 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 P...), there were significant increases in the relative mRNA expression of M... and the cardiac type β-adrenergic receptors (β1AR, β2aAR, and β2bAR) at 4 dpf. The hypoxic bradycardia was abolished (at 40 Torr P...) or significantly attenuated (at 30 Torr P...) in larvae experiencing M... receptor knockdown (using morpholino antisense oligonucleotides). Sham-injected larvae exhibited typical hypoxic bradycardia in both hypoxic regimens. The expression of β1AR, bβaAR, β2bAR, and M... mRNA was altered at various stages between 1 and 4 dpf in larvae experiencing M... receptor knockdown. Interestingly, M... receptor knockdown revealed a cardioinhibitory role for the β...-adrenergic receptor. This is the first study to demonstrate a specific role of the M... muscarinic receptor in the initiation of hypoxic bradycardia in fish. (ProQuest: ... denotes formulae/symbols omitted.)