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Altered Repolarization Reserve in Failing Rabbit Ventricular Myocytes
| Content Provider | Scilit |
|---|---|
| Author | Hegyi, Bence Bossuyt, Julie Ginsburg, Kenneth S. Mendoza, Lynette M. Talken, Linda Ferrier, William T. Pogwizd, Steven M. Izu, Leighton T. Chen-Izu, Ye Bers, Donald M. |
| Copyright Year | 2018 |
| Description | Journal: Circulation: Arrhythmia and Electrophysiology Background: Electrophysiological remodeling and increased susceptibility for cardiac arrhythmias are hallmarks of heart failure (HF). Ventricular action potential duration (APD) is typically prolonged in HF, with reduced repolarization reserve. However, underlying K$ ^{+}$ current changes are often measured in nonphysiological conditions (voltage clamp, low pacing rates, cytosolic Ca$ ^{2+}$ buffers). Methods and Results: We measured the major K$ ^{+}$ currents ( I$ _{Kr}$ , I$ _{Ks}$ , and I$ _{K1}$ ) and their Ca$ ^{2+}$ - and β-adrenergic dependence in rabbit ventricular myocytes in chronic pressure/volume overload–induced HF (versus age-matched controls). APD was significantly prolonged only at lower pacing rates (0.2–1 Hz) in HF under physiological ionic conditions and temperature. However, when cytosolic Ca$ ^{2+}$ was buffered, APD prolongation in HF was also significant at higher pacing rates. Beat-to-beat variability of APD was also significantly increased in HF. Both I$ _{Kr}$ and I$ _{Ks}$ were significantly upregulated in HF under action potential clamp, but only when cytosolic Ca$ ^{2+}$ was not buffered. CaMKII (Ca$ ^{2+}$ /calmodulin-dependent protein kinase II) inhibition abolished I$ _{Ks}$ upregulation in HF, but it did not affect I$ _{Kr}$ . I$ _{Ks}$ response to β-adrenergic stimulation was also significantly diminished in HF. I$ _{K1}$ was also decreased in HF regardless of Ca$ ^{2+}$ buffering, CaMKII inhibition, or β-adrenergic stimulation. Conclusions: At baseline Ca$ ^{2+}$ -dependent upregulation of I$ _{Kr}$ and I$ _{Ks}$ in HF counterbalances the reduced I$ _{K1}$ , maintaining repolarization reserve (especially at higher heart rates) in physiological conditions, unlike conditions of strong cytosolic Ca$ ^{2+}$ buffering. However, under β-adrenergic stimulation, reduced I$ _{Ks}$ responsiveness severely limits integrated repolarizing K$ ^{+}$ current and repolarization reserve in HF. This would increase arrhythmia propensity in HF, especially during adrenergic stress. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5813707/pdf https://www.ahajournals.org/doi/reader/10.1161/CIRCEP.117.005852 |
| Ending Page | e005852 |
| Page Count | 1 |
| Starting Page | e005852 |
| ISSN | 19413149 |
| e-ISSN | 19413084 |
| DOI | 10.1161/circep.117.005852 |
| Journal | Circulation: Arrhythmia and Electrophysiology |
| Issue Number | 2 |
| Volume Number | 11 |
| Language | English |
| Publisher | Ovid Technologies (Wolters Kluwer Health) |
| Publisher Date | 2018-02-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Circulation: Arrhythmia and Electrophysiology Peripheral Vascular Disease Calcium/calmodulin-dependent Protein Kinase Ii Electrophysiology Potassium Channels |
| Content Type | Text |
| Resource Type | Article |
| Subject | Physiology (medical) Cardiology and Cardiovascular Medicine |
