Skip Navigation

Cardiovascular Research 1999 41(3):620-628; doi:10.1016/S0008-6363(98)00281-8
© 1999 by European Society of Cardiology
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
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 Saeki, T.
Right arrow Articles by Pappano, A. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Saeki, T.
Right arrow Articles by Pappano, A. J.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Copyright © 1999, European Society of Cardiology

Inositol-1,4,5-trisphosphate increases contractions but not L-type calcium current in guinea pig ventricular myocytes

Tomoaki Saeki1,1, Jian-Bing Shen and Achilles J. Pappano*

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

* Corresponding author. Tel.: +860-679-2410; fax: +860-679-3693; e-mail: pappano@nsol.uchc.edu

Objective: We studied the effects of intracellularly applied inositol-1,4,5-trisphosphate (InsP3) to test the hypothesis that InsP3 is a messenger for stimulation of L-type calcium current (ICa(L)) and contractions by muscarinic agonists. Methods: Voltage clamp pulses elicited ICa(L) that evoked contractions recorded with an edge detector in single guinea pig ventricular myocytes superfused with Tyrode’s solution (36°C). InsP3 or cyclic AMP (cAMP) was dialyzed into the cell at selected times via the patch electrode. Results: InsP3 (1–10 µM) transiently increased isotonic contractions when applied for 4–5 min; higher concentrations (50–300 µM) caused a sustained decrease in contractions. InsP3 had no effect on ICa(L) at any concentration tested. Caffeine (10 mM)-induced contractures were increased and decreased, respectively, at 3 and 100 µM InsP3. Pentosan polysulfate (50 µg/ml), an InsP3 receptor antagonist, opposed the increased contractions by InsP3. Intrapipette cyclic AMP (10–300 µM) caused sustained increases of ICa(L) and contractions. Cyclic AMP, but not InsP3, also increased ICa(L) when intrapipette Cs+ suppressed K+ currents. Conclusions: Increased myocyte shortening at low InsP3 concentrations accords with receptor-initiated sarcoplasmic reticulum Ca2+ release. The transient stimulation of contractions at low concentrations and the sustained reduction of contractions at high concentrations are not consistent with a role for InsP3 in the persistent increase of contractions by muscarinic agonist in ventricular muscle and myocytes. The failure of InsP3 to change ICa(L) when contractions were increased or decreased militates against the L-type calcium channel being an effector of InsP3.

KEYWORDS Guinea pig; Ventricular myocytes; Cell contractions; Sarcoplasmic reticulum; InsP3; Excitation–contraction coupling; Intracellular dialysis; L-type Ca2+ current; Cyclic AMP

1 Present address: Third Department of Internal Medicine, Nagoya City University Medical School, 1 Kawasumi Mizuko-cho, Mizuko-ku, Nagoya 467, Japan.


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.