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(Circulation Research. 2003;93:e87.)
© 2003 American Heart Association, Inc.

Letter to the Editor

On the Role of the cAMP Response Element Binding Protein in Long-Term Cardiac Memory

Kornelis W. Patberg, Michael R. Rosen

Center for Molecular Therapeutics, Department of Pharmacology, College of Physicians and Surgeons, of Columbia University, New York, NY, mrr1@columbia.edu

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

To the Editor:

Cardiac memory (CM) has been investigated extensively over the last decades.^1–3 Whereas early studies focused on electrotonus as a central determinant of cardiac memory,³ more recent work has considered changes in ion channels driven by to-be-determined transcriptional events.^4,5 However, any transcriptional mechanisms involved remained largely unidentified. In the September 5 issue of the journal, we reported our first study investigating transcriptional mechanisms of CM.⁶ Based on previously shown parallels between CM and memory in the CNS,⁷ which incorporates the cAMP response element binding protein (CREB) as an important transcription factor,⁸ we investigated the role of CREB in CM. Briefly, using 2 hours of ventricular pacing (VP) to induce short-term CM (STCM), we observed a decrease in nuclear CREB, with phosphorylated CREB levels remaining equal. This decrease was most marked close to the pacing electrode. We also showed reduced binding of nuclear proteins to CRE in dogs in which LTCM was induced by 3 weeks of VP and demonstrated binding of nuclear proteins to a CRE-like element in the Kv4.3 promoter.

An erudite editorial by Folco et al⁹ in the same issue of the journal notes that several members of the CREB family of transcription factors (including CREM and ATF-1) can compensate for a loss of CREB. They also state that a 50% reduction in CREB is not necessarily adequate to cause loss of function. We fully agree with both points, and accordingly never stated that the 50% CREB reduction observed during 2 hours of VP is responsible . . . [Full Text of this Article]