Cardiac Memory Is Associated With Decreased Levels of the Transcriptional Factor CREB Modulated by Angiotensin II and Calcium
- 5 September 2003
- journal article
- research article
- Published by Wolters Kluwer Health in Circulation Research
- Vol. 93 (5) , 472-478
- https://doi.org/10.1161/01.res.0000088785.24381.2f
Abstract
Cardiac memory (CM) has short- (STCM) and long-term (LTCM) components modulated by calcium and angiotensin II. LTCM is associated with reduced I to and Kv4.3 mRNA levels. Because the cAMP response element binding protein, CREB, contributes to CNS memory transcription, we hypothesized that it might be a transcriptional factor in CM, influenced by calcium and angiotensin II. We studied STCM in dogs that were AV sequentially paced (AVP) for 2 hours or sham-operated. STCM was evaluated with ECG and vectorcardiogram (VCG), and subepicardial biopsies were taken at 5 to 120 minutes and investigated for CREB. LTCM was studied in dogs paced for 3 weeks and in sham controls. At 3 weeks the heart was excised, biopsies obtained, and CRE binding tested. STCM induction occurred in AVP dogs but not in sham or AVP dogs treated with saralasin or nifedipine. Nuclear CREB was significantly decreased at 2 hours in the AVP no-drug group only. LTCM dogs manifested reduced binding of nuclear proteins to CRE, and CRE binding activity in the promoter region of Kv4.3. In conclusion, there is an association between STCM induction and decreased nuclear CREB that is angiotensin-modulated and calcium-dependent. Moreover, the decreased CRE binding after 3 weeks of AVP combined with CRE binding activity in the Kv4.3 promoter can explain the Kv4.3 mRNA and I to downregulation that characterize LTCM.Keywords
This publication has 24 references indexed in Scilit:
- Role of L-Type Calcium Channels in Pacing-Induced Short-Term and Long-Term Cardiac Memory in Canine HeartCirculation, 2003
- The Molecular Biology of Memory Storage: A Dialogue Between Genes and SynapsesScience, 2001
- A Role for the Renin‐Angiotensin System in the Evolution of Cardiac MemoryJournal of Cardiovascular Electrophysiology, 1999
- The heart remembersCardiovascular Research, 1998
- Cloning and sequence analysis of the human β1-adrenergic receptor 5′-flanking promoter regionBiochimica et Biophysica Acta (BBA) - Gene Structure and Expression, 1993
- Identification of a highly conserved region at the 5′ flank of the phospholamban geneBiochemical and Biophysical Research Communications, 1992
- Tissue‐specific expression of mRNAs encoding α‐ and β‐catalytic subunits of protein phosphatase 2AFEBS Letters, 1988
- Electrotonic modulation of the T wave and cardiac memoryThe American Journal of Cardiology, 1982
- Effects of angiotensin II on membrane current in cardiac Purkinje fibersJournal of Molecular and Cellular Cardiology, 1981
- A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye bindingAnalytical Biochemistry, 1976