HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: 294/5/H2031    most recent 01357.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Song, Y. Articles by Belardinelli, L. Search for Related Content PubMed PubMed Citation Articles by Song, Y. Articles by Belardinelli, L.

An increase of late sodium current induces delayed afterdepolarizations and sustained triggered activity in atrial myocytes

¹Division of Cardiovascular Medicine, University of Florida, Gainesville, Florida; and ²CV Therapeutics, Inc., Palo Alto, California

Submitted 21 November 2007 ; accepted in final form 28 February 2008

This study determined the role of a slowly inactivating component of sodium current (I_Na), late I_Na, to induce delayed afterdepolarizations (DADs) and triggered activity. We hypothesized that an increase of late I_Na may induce not only early afterdepolarizations (EADs), but also intracellular calcium overload and DADs. Guinea pig atrial myocytes were studied using the whole cell patch-clamp technique. Anemone toxin II (ATX-II) (5–10 nmol/l) was used to enhance late I_Na. Ranolazine (10 µmol/l) and TTX (2 µmol/l) were applied to block ATX-II-induced late I_Na. ATX-II prolonged action potential duration and induced EADs. In the continuous presence of ATX-II, following the appearance of EADs, both DADs and sustained triggered activity occurred. Triggered activity was abolished and DADs were reduced by either ranolazine or TTX. Consistent with induction of DADs, ATX-II induced the transient inward current (I_TI). The amplitude of I_TI was significantly reduced by ranolazine. ATX-II induced only EADs, but no DADs, in the presence of the sodium-calcium exchange inhibitor KB-R7943 or the sarcoplasmic reticulum calcium release channel inhibitor ryanodine, or when the calcium chelator EGTA or BAPTA was included in the pipette solution. In conclusion, an increase of late I_Na, in addition to inducing EADs, can cause cellular calcium overload and induce DADs and sustained triggered activity in atrial myocytes. The data reveal that an increase of late I_Na is a novel mechanism for initiation of atrial arrhythmic activity.

action potential; calcium overload; transient inward current

This article has been cited by other articles:

				L.-H. Xie, F. Chen, H. S. Karagueuzian, and J. N. Weiss Oxidative Stress-Induced Afterdepolarizations and Calmodulin Kinase II Signaling Circ. Res., January 2, 2009; 104(1): 79 - 86. [Abstract] [Full Text] [PDF]