This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted 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 Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Josephson, I. R. Articles by Wilde, A. A.M. Search for Related Content PubMed PubMed Citation Articles by Josephson, I. R. Articles by Wilde, A. A.M. Related Collections Arrythmias-basic studies Ion channels/membrane transport Arrhythmias, clinical electrophysiology, drugs

(Circulation. 2006;113:e408.)
© 2006 American Heart Association, Inc.

Correspondence

Letter Regarding Article by Darbar et al, "Unmasking of Brugada Syndrome by Lithium"

Ira R. Josephson, PhD; W. Jonathan Lederer, MD, PhD; Hali A. Hartmann, PhD

Institute of Molecular Cardiology, Medical Biotechnology Center, University of Maryland Biotechnology Institute, Baltimore, Md, Josephso@umbi.umd.edu

An extract of the first 250 words of the full text is provided, because this article has no abstract.

To the Editor:

It was with great interest that we read the study by Darbar and colleagues in a recent issue of Circulation.¹ The authors reported on 2 patients who developed the Brugada ECG pattern after administration of lithium, a commonly used drug not previously reported to block cardiac Na⁺ channels. Surprisingly, Darbar and colleagues found that LiCl caused a concentration-dependent block of peak I_Na, with an IC₅₀ of 6.8±0.4 µmol/L, a level 100 times below the therapeutic range (&1 mmol/L). They concluded that lithium is a potent blocker of cardiac Na⁺ channels and may unmask patients with the Brugada syndrome.

It is well known from numerous studies (conducted during the last 3 decades) that Li⁺ ions permeate Na⁺ channels, as well as do Na⁺ ions, in a variety of excitable cell types.² Although there is little information available concerning lithium permeation through cardiac Na⁺ channels, there is no reason a priori to expect a lithium block, as the selectivity sequence is largely conserved among Na⁺ channels from different tissues.³ Amazed by the unusual and puzzling findings of Darbar et al (that Li⁺ ion acts as a blocker of the cardiac Na⁺ channel), we conducted our own experiments on whole-cell Na⁺ currents in either human embryonic kidney cells stably expressing cardiac Na⁺ channels (SCN5a; Nav1.5) or adult rat ventricular myocytes. We used experimental conditions similar to those of Darbar et al. We found that the peak Na⁺ currents after administration of 10 µmol/L LiCl or even 100 µmol/L . . . [Full Text of this Article]

Dawood Darbar, MD; Tao Yang, MD, PhD; Dan M. Roden, MD

Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, Tenn, dawood.darbar@vanderbilt.edu

Keith Churchwell, MD

Division of Cardiovascular Medicine, Vanderbilt University School of Medicine, Nashville, Tenn

Arthur A.M. Wilde, MD, PhD

Cardiology Department, Academic Medical Center, Amsterdam, The Netherlands