Skip Navigation

European Heart Journal 1991 12(Supplement F):70-75; doi:10.1093/eurheartj/12.suppl_F.70
Copyright © 1991 by the European Society of Cardiology.
This Article
Right arrow Full Text (PDF)
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Pappano, A. J.
Right arrow Articles by Mubagwa, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Pappano, A. J.
Right arrow Articles by Mubagwa, K.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 1991 The European Society of Cardiology

Muscarinic agonist-induced actions on potassium and calcium channels in atrial myocytes: differential desensitization

A. J. Pappano and K. Mubagwa

Department of Pharmacology University of Connecticut Health Center Farmington, CT 06030, USA

Correspondence: A. J. Pappano, Department of Pharmacology, University of Connecticut Health Center, Farmington, CT 06030, U.S.A.

Desensitization to the effects of acetylcholine (ACh) or carbachol (CCh) on ACh-regulated potassium current (IK(ACh)) and the voltage-dependent L-type, calcium current (ICa(L)) was studied in single guinea-pig atrial cells under voltage clamp at room temperature (22–24°C). At a holding potential of –40mV, CCh (100µm) activated IK(ACh) repeatedly and reproducibly when applied for 15-s periods with 60s intervals between applications. Prolonged (lOmin) exposure to CCh caused a time-dependent decline of IK(ACh) and a marked reduction (desensitization) of the response to subsequent application of CCh. In the absence of guanosine triphosphate (GTP) in the pipette, only partial resensitization occurred within 20min after CCh washout. The desensitization to CCh could also be obtained when adenosine (20µm) was used to activate this current. Therefore, this desensitization must be heterologous. In the presence of isoproterenol (ISO, 3 µm), 1Ca(L) increased. Acetylcholine continued to inhibit this current at a time when its activation of IK(ACh) had become desensitized. Muscarinic inhibition of 1Ca(L) eventually desensitized but only after IK(ACh) desensitization had occurred. Because of its heterologous nature, as well as of the ability of ACh to desensitize in the presence of intrapipette dextran, which is reported to inhibit β-adrenergic receptor kinase (βARK), it seems unlikely that βARK-dependent phosphorylation of the muscarinic receptor (mAChR) accounted for desensitization. The differential desensitization time course is consistent with the hypothesis that different subunits of G1 the inhibitory guanine nucleotide binding protein, not only transduce the agonist effects of ACh on IK(ACh) and ICa(L) but are also subjected to different inactivation/regulation processes.

Key Words: Muscarinic agonist • adenosine • IK(ACh,ADO) • ICa(L) • desensitization • guinea pig atria • whole cell voltage clamp • guanine nucleotides


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.