PlumX Metrics
Embed PlumX Metrics

Regulation of heart contractility by M and M muscarinic receptors: Functional studies using muscarinic receptor knockout mouse

Neuromethods, ISSN: 1940-6045, Vol: 107, Page: 235-259
2016
  • 3
    Citations
  • 0
    Usage
  • 5
    Captures
  • 0
    Mentions
  • 0
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

Book Chapter Description

To investigate the functional roles of M and M muscarinic receptors in mouse atria, wild-type mice, muscarinic M or M single receptor knockout mice (M KO, M KO), and M and M muscarinic receptor double knockout mice (M /M KO) were used for pharmacological and molecular biological approaches. Effects of carbachol on spontaneous contraction (right atrium) or electrically evoked contraction (left atrium) were examined in the isolated atria of the respective mice. Presence of muscarinic receptor subtype mRNAs and proteins was determined by real time RT-PCR using specifi c primers and immunohistochemistry using specifi c anti-M and anti-M receptor antibodies. Quantitative real-time RT-PCR analysis showed that M 2 receptor mRNA was expressed dominantly in mouse atria but that the M, M, M, and M receptor subtypes were also expressed at low levels. Carbachol decreased the frequency of spontaneous beating in right atria of mice through activation of the M receptor subtype. In left atria of wild-type mice, carbachol decreased the amplitude of electrical field stimulation (EFS)-evoked contractions (M receptors), but this inhibition was transient and was followed by a gradual increase in contraction amplitude (M receptors). Cyclooxygenase-2 (COX-2) and prostaglandins in the endocardial endothelium were involved in the M receptor-mediated positive inotropic actions. In conclusion, the present studies using isolated atria of muscarinic receptor knockout mice demonstrated that myocardial M receptors mediate negative chronotropic/inotropic actions and that M muscarinic receptors mediate positive chronotropic/inotropic actions in mouse atria. Physiologically, M receptor-mediated excitatory cardiac effects might dampen the inhibitory effects of M receptor activation on cardiac contractility.

Bibliographic Details

Takio Kitazawa; Hiroki Teraoka; Nao Harada; Kenta Ochi; Tatsuro Nakamura; Koichi Asakawa; Shinya Kanegae; Noriko Yaosaka; Toshihiro Unno; Sei Ichi Komori; Masahisa Yamada

Springer Science and Business Media LLC

Neuroscience; Biochemistry, Genetics and Molecular Biology; Pharmacology, Toxicology and Pharmaceutics; Medicine

Provide Feedback

Have ideas for a new metric? Would you like to see something else here?Let us know