Wang Yanggan, Xu Huaying, Kumar Rajiv, Tipparaju Srinivas M, Wagner Mary B, Joyner Ronald W
Department of Pediatrics, Todd Franklin Cardiac Research Laboratory, Sibley Heart Center, Emory University, 2040 Ridgewood Drive NE, Atlanta, GA 30322, USA.
J Mol Cell Cardiol. 2003 Sep;35(9):1083-92. doi: 10.1016/s0022-2828(03)00200-1.
Knowledge of postnatal modulation of I(to) in human atrial myocytes is quite limited. The present study investigated the differences in I(to) properties between neonatal and adult human atrial myocytes.
Atrial myocytes were dissociated enzymatically from biopsies of human right atrial appendage. I(to) and action potentials were recorded by whole-cell patch-clamp technique. The expressed protein levels of Kv4.3 and KChIP2 in atrial tissue were detected by western blot technique.
I(to) was present in all atrial cells (n = 37) from 10 neonatal patients (2.5-7 months). The mean value of I(to) density in neonatal atrial cells was significantly larger than in adult atrial cells. The time constants for I(to) current decay were significantly faster for neonatal cells, compared to adult cells. I(to) recovery from inactivation at holding potential of - 80 mV was significantly slower for neonatal atrial cells than for adult atrial cells. There was no difference in the voltage dependence of I(to) activation between neonatal and adult cells. The voltage-dependent inactivation slope factor was smaller for neonatal compared to adult atrial cells. A more significant frequency-dependent suppression of I(to) peak current and a more significant lengthening of APD(30) were observed in neonatal atrial cells compared to adult atrial cells. Western blots showed both Kv4.3 and KChIP2 are expressed in neonatal atria, but with significantly higher level of Kv4.3 and lower level of KChIP2 protein compared to adult.
There are significant differences in the properties of I(to) between neonatal and adult human atrial cells, including a larger current density, faster inactivation and slower recovery from inactivation in the neonatal atrial cells. The physiological differences of I(to) are consistent with the different expression protein levels of Kv4.3 and KChIP2.
