| First Author | Li J | Year | 2004 |
| Journal | Am J Physiol Heart Circ Physiol | Volume | 287 |
| Issue | 6 | Pages | H2790-802 |
| PubMed ID | 15271672 | Mgi Jnum | J:95753 |
| Mgi Id | MGI:3527297 | Doi | 10.1152/ajpheart.00114.2004 |
| Citation | Li J, et al. (2004) Transgenic upregulation of IK1 in the mouse heart leads to multiple abnormalities of cardiac excitability. Am J Physiol Heart Circ Physiol 287(6):H2790-802 |
| abstractText | To assess the functional significance of upregulation of the cardiac current (IK1), we have produced and characterized the first transgenic (TG) mouse model of IK1 upregulation. To increase IK1 density, a pore-forming subunit of the Kir2.1 (green fluorescent protein-tagged) channel was expressed in the heart under control of the alpha-myosin heavy chain promoter. Two lines of TG animals were established with a high level of TG expression in all major parts of the heart: line 1 mice were characterized by 14% heart hypertrophy and a normal life span; line 2 mice displayed an increased mortality rate, and in mice < or =1 mo old, heart weight-to-body weight ratio was increased by >100%. In adult ventricular myocytes expressing the Kir2.1-GFP subunit, IK1 conductance at the reversal potential was increased approximately 9- and approximately 10-fold in lines 1 and 2, respectively. Expression of the Kir2.1 transgene in line 2 ventricular myocytes was heterogeneous when assayed by single-cell analysis of GFP fluorescence. Surface ECG recordings in line 2 mice revealed numerous abnormalities of excitability, including slowed heart rate, premature ventricular contractions, atrioventricular block, and atrial fibrillation. Line 1 mice displayed a less severe phenotype. In both TG lines, action potential duration at 90% repolarization and monophasic action potential at 75-90% repolarization were significantly reduced, leading to neuronlike action potentials, and the slow phase of the T wave was abolished, leading to a short Q-T interval. This study provides a new TG model of IK1 upregulation, confirms the significant role of IK1 in cardiac excitability, and is consistent with adverse effects of IK1 upregulation on cardiac electrical activity. |
