Dr. Barbara Rosati

T6-122 HSC
Phone: (631)-444.7350
E-Mail: Barbara.Rosati.1@stonybrook.edu

Differential expression of ion channel genes underlies differences in the action potential shapes in cardiac myocytes isolated from different regions of the heart (e.g. ventricular myocytes versus Purkinje fibers) and is a major contributor to the functional specialization of the cardiac cells. Nonetheless, very little is currently known about the regulation of ion channel gene expression in the adult heart. The KChIP2 gene encodes a calcium-binding protein, which associates with K+ channels of the Kv4 family modifying their biophysical properties and facilitating their targeting to the cell membrane1,2. We have recently proposed that uneven expression of the KChIP2 gene across the cardiac left ventricle is responsible for the heterogeneity in the transient outward K+ current (Ito) density3. A deeper analysis of the KChIP2 gene and Ito expression across the ventricles shows a very complex pattern4. We are currently investigating the mechanisms that govern this distribution.
Understanding how the expression of ion channel genes is controlled is a crucial question in cardiac physiology since disruption of the normal pattern of ion channel expression, occurring for example during pathological conditions, can contribute to the genesis of arrhythmias.

1. An et al. (2000). Modulation of A-type potassium channels by a family of calcium sensors. Nature. 403:553-6
2. Shibata et al. (2003). A fundamental role for KChIPs in determining the molecular properties and trafficking of Kv4.2 potassium channels. J Biol Chem., in press.
3. Rosati et al. (2001). Regulation of KChIP2 potassium channel beta subunit gene expression underlies the gradient of transient outward current in canine and human ventricle. J Physiol. 533:119-25.
4. Rosati et al. (2003). Concordant expression of KChIP2 mRNA, protein and transient outward current throughout the canine ventricle. J. Physiol. 548:815-22.