The cardiac homeodomain transcription factor Irx5 is required to maintain the mouse transmural ventricular repolarization gradient.
Published: 2005
Language: eng
Number of pages: 106
Description: Ventricular repolarization relies on a transmural gradient of potassium currents. In many species, this electrical heterogeneity is established by the gradient of the fast, transient outward K+ current (I to,f) that is significantly higher in epicardial myocardium than endocardial myocardium. It is not known how this gradient is established in the heart. Here it is shown that in mice lacking the homeodomain containing transcription factor Irx5, the cardiac transmural repolarization gradient is abolished, resulting in altered ECG patterns and increased susceptibility to arrhythmias. Loss of Irx5 also results in a selective increase of the major cardiac repolarization current, Ito,f, in endocardial myocardium due to increased Kv4.2 gene and protein expression. Irx5 is expressed in the myocardium, in an endocardial-to-epicardial gradient and can directly act on the Kv4.2 promoter, but requires additional cofactors to counter its activation. Thus, an inverse gradient of Irx5 is required to maintain the cardiac repolarization gradient.
Notes: Source: Masters Abstracts International, Volume: 44-01, page: 0228.

Thesis (M.Sc.)--University of Toronto, 2005.

Electronic version licensed for access by U. of T. users.

ROBARTS MICROTEXT copy on microfiche.