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(Circulation Research. 2008;103:681.)
© 2008 American Heart Association, Inc.

Editorials

NFAT-Dependent Excitation–Transcription Coupling in Heart

Luis F. Santana

From the Department of Physiology & Biophysics, University of Washington, Seattle.

Correspondence to Luis F. Santana, Department of Physiology & Biophysics, University of Washington, Box 357290, Seattle, WA 98195. E-mail santana@u.washington.edu

See related article, pages 733–742

Key Words: arrhythmias • calcium • L-type Ca²⁺ channels • I_to

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

	Introduction

 
Two articles from the laboratory of Stanley Nattel,^1,2 one article in this issue of Circulation Research and an article in an upcoming issue of the journal, address an important, long-standing question in cardiac physiology: what are the molecular mechanisms underlying rate-dependent changes in the function of voltage-gated K⁺ and L-type Ca²⁺ channels in ventricular and atrial myocytes? Through a series of elegant experiments, they provide an interesting and unexpected answer to this difficult conundrum. In many ways, these 2 studies are excellent examples of how implementation of the problem-solving approach of Prof George Polya³ remains an invaluable tool to resolve complex problems in biology. Accordingly, I use a "Polyaesque" framework below to illustrate the importance and broad implications of the work by Xiao et al¹ and Qi et al.²

	Step 1: Defining and Understanding the Problem

 
Multiples studies indicate that chronic increases in heart rate are associated with changes in the waveform of the action potential (AP) of atrial and ventricular myocytes. In atria, sustained, high-frequency electric activation rates are associated with shortening of the AP of atrial myocytes.^4,5 This results in a decrease in the refractory period of the AP of atrial myocytes, which could increase the probability of atrial fibrillation, the most common cardiac arrhythmia. Interestingly, a decrease in depolarizing L-type Ca²⁺ channel current (I_Ca) function has been linked to decreased atrial AP duration during tachycardia.^6,7 Downregulation of the transcript and protein levels of the pore-forming subunit of L-type Ca²⁺ channels (Cav1.2) underlie decreased I_Ca function during atrial tachycardia and fibrillation.

Like atrial . . . [Full Text of this Article]

Related Article:

Mechanisms Underlying Rate-Dependent Remodeling of Transient Outward Potassium Current in Canine Ventricular Myocytes

Ling Xiao, Pierre Coutu, Louis R. Villeneuve, Artavazd Tadevosyan, Ange Maguy, Sabrina Le Bouter, Bruce G. Allen, and Stanley Nattel
Circ. Res. 2008 103: 733-742. [Abstract] [Full Text] [PDF]