Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Molecular Pharmacology
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Molecular Pharmacology

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Visit molpharm on Facebook
  • Follow molpharm on Twitter
  • Follow molpharm on LinkedIn
Research ArticleArticle

Identification and Characterization of Multiple Subtypes of Muscarinic Acetylcholine Receptors and Their Physiological Functions in Canine Hearts

Hong Shi, Huizhen Wang and Zhiguo Wang
Molecular Pharmacology March 1999, 55 (3) 497-507;
Hong Shi
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Huizhen Wang
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Zhiguo Wang
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

M2 receptors have long been believed to be the only functional subtype of muscarinic acetylcholine receptor (mAChR) in the heart, although recent studies have provided evidence for the presence of other subtypes. We performed a detailed study to clarify this issue. In the presence of tetramethylammonium (1 μM to 10 mM), a novel K+ current with both delayed rectifying and inward rectifying properties (IKTMA) was activated in single canine atrial myocytes. 4-Aminopyridine (0.05–2 mM) also induced a K+ current (IK4AP) with characteristics similar to but distinct from those of IKTMA. Both IKTMAand IK4AP were abolished by 1 μM atropine. IK4AP, but not IKTMA, was minimized by treatment with pertussis toxin. IKTMA was markedly decreased by 4-diphenylacetoxy-N-methylpiperidine methiodide (a selective antagonist for M3 subtype) but was not altered by pirenzepine (for M1), methoctramine (for M2), and tropicamide (for M4). Tropicamide substantially reduced IK4AP, but the antagonists for other mAChR subtypes had no effects on IK4AP. By comparison, IKACh (ACh-induced K+ current) was significantly depressed by methoctramine but was unaltered by other antagonists. Results from displacement binding of [methyl-3H]N-scopolamine methyl chloride with pirenzepine, methoctramine, 4-diphenylacetoxy-N-methylpiperidine methiodide, or tropicamide revealed the coexistence of multiple mAChR subtypes in canine atrium. Cloning of cDNA fragments and detection of mRNAs coding for M2, M3, and M4 provided further supporting evidence. Our results suggest that 1) multiple subtypes of mAChRs (M2/M3/M4) coexist in the dog heart and 2) different subtypes of mAChRs are coupled to different K+ channels. Our findings represent the first functional evidence for the physiological role of cardiac M3 and M4 receptors.

Footnotes

  • Send reprint requests to: Zhiguo Wang, Ph.D, Research Center, Montreal Heart Institute, 5000 Bélanger Street East, Montreal, Quebec, Canada H1T 1C8. E-mail:wangz{at}icm.umontreal.ca

  • 1 This work was supported in part by the Medical Research Council of Canada, the Heart and Stroke Foundation of Quebec, an Establishment Grant for young investigators from the Fonds de Recherche en Santé du Québec (Z.W.), and the Fonds de Recherche de l’Institut de Cardiologie de Montréal. Z.W. is a Heart and Stroke Foundation of Canada Research Scholar.

  • Abbreviations:
    mAChR
    muscarinic acetylcholine receptor
    ACh
    acetylcholine
    TMA
    tetramethylammonium
    IKTMA
    tetramethylammonium-induced K+ currents
    PTX
    pertussis toxin
    4AP
    4-aminopyridine
    IK4AP
    4-aminopyridine-induced K+ currents
    PZ
    pirenzepine
    Meth
    methoctramine
    4-DAMP
    4-diphenylacetoxy-N-methylpiperidine methiodide
    p-F-HHSiD
    hexahydro-sila-difenidol hydrochloride,p-fluoro analog
    Trop
    tropicamide
    [3H]NMS
    [methyl-3H]N-scopolamine methyl chloride
    pKi
    equilibrium dissociation constant
    RT
    reverse transcription
    PCR
    polymerase chain reaction
    IKr
    rapid component of delayed rectifier K+ current
    IKs slow component of delayed rectifier K+ current.
    • Received June 1, 1998.
    • Accepted December 7, 1998.
  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

MolPharm articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Molecular Pharmacology: 55 (3)
Molecular Pharmacology
Vol. 55, Issue 3
1 Mar 1999
  • Table of Contents
  • About the Cover
  • Index by author
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Molecular Pharmacology article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Identification and Characterization of Multiple Subtypes of Muscarinic Acetylcholine Receptors and Their Physiological Functions in Canine Hearts
(Your Name) has forwarded a page to you from Molecular Pharmacology
(Your Name) thought you would be interested in this article in Molecular Pharmacology.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

Identification and Characterization of Multiple Subtypes of Muscarinic Acetylcholine Receptors and Their Physiological Functions in Canine Hearts

Hong Shi, Huizhen Wang and Zhiguo Wang
Molecular Pharmacology March 1, 1999, 55 (3) 497-507;

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Research ArticleArticle

Identification and Characterization of Multiple Subtypes of Muscarinic Acetylcholine Receptors and Their Physiological Functions in Canine Hearts

Hong Shi, Huizhen Wang and Zhiguo Wang
Molecular Pharmacology March 1, 1999, 55 (3) 497-507;
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Differential Drug Effects on Homo/Heteromeric hERG Channels
  • ACKR3 Senses CXCR4 Activation Through GRK Phosphorylation
  • Analgesic Effects and Mechanisms of Licochalcones
Show more Article

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About Molecular Pharmacology
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Journal of Pharmacology and Experimental Therapeutics
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0111 (Online)

Copyright © 2023 by the American Society for Pharmacology and Experimental Therapeutics