Ion Channel Remodeling Is Related to Intraoperative Atrial Effective Refractory Periods in Patients With Paroxysmal and Persistent Atrial Fibrillation
| Autor: | JG Grandjean, AE Tuinenburg, Mirian Wietses, van Isabelle Gelder, van Wiekert Gilst, Robert G. Tieleman, Hjgm Crijns, Bjjm Brundel, Robert H. Henning |
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| Rok vydání: | 2001 |
| Předmět: |
medicine.medical_specialty
Potassium Channels Calcium Channels L-Type Refractory period hERG Gene Expression Intraoperative Period Physiology (medical) Internal medicine Atrial Fibrillation medicine Humans Sinus rhythm RNA Messenger Fibrillation Voltage-dependent calcium channel biology business.industry Calcium channel Atrial fibrillation Middle Aged medicine.disease Potassium channel Electrophysiology Endocrinology Cardiology biology.protein medicine.symptom Cardiology and Cardiovascular Medicine business Ion Channel Gating |
| Zdroj: | Circulation. 103:684-690 |
| ISSN: | 1524-4539 0009-7322 |
| DOI: | 10.1161/01.cir.103.5.684 |
| Popis: | Background —Sustained shortening of the atrial effective refractory period (AERP), probably due to reduction in the L-type calcium current, is a major factor in the initiation and maintenance of atrial fibrillation (AF). We investigated underlying molecular changes by studying the relation between gene expression of the L-type calcium channel and potassium channels and AERP in patients with AF. Methods and Results —mRNA and protein expression were determined in the left and right atrial appendages of patients with paroxysmal (n=13) or persistent (n=16) AF and of 13 controls in sinus rhythm using reverse transcription polymerase chain reaction and slot-blot, respectively. The mRNA content of almost all investigated ion channel genes was reduced in persistent but not in paroxysmal AF. Protein levels for the L-type Ca 2+ channel and 5 potassium channels (Kv4.3, Kv1.5, HERG, minK, and Kir3.1) were significantly reduced in both persistent and paroxysmal AF. Furthermore, AERPs were determined intraoperatively at 5 basic cycle lengths between 250 and 600 ms. Patients with persistent and paroxysmal AF displayed significant shorter AERPs. Protein levels of all ion channels investigated correlated positively with the AERP and with the rate adaptation of AERP. Patients with reduced ion channel protein expression had a shorter AERP duration and poorer rate adaptation. Conclusions —AF is predominantly accompanied by decreased protein contents of the L-type Ca 2+ channel and several potassium channels. Reductions in L-type Ca 2+ channel correlated with AERP and rate adaptation, and they represent a probable explanation for the electrophysiological changes during AF. |
| Databáze: | OpenAIRE |
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