Submitted on April 4, 2007
Accepted on September 20, 2007
HETEROGENEITY OF IK1 IN THE MOUSE HEART
Brian K. Panama1, Meredith McLerie1, and Anatoli N. Lopatin1*
1 Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, United States
* To whom correspondence should be addressed. E-mail: alopatin{at}umich.edu.
Previous studies have shown that cardiac IK1 channels are heteromers of distinct Kir2 subunits, and suggested that species and tissue-dependent expression of these subunits may underlie variability of IK1. In this study, we investigated the contribution of the slowly activating Kir2.3 subunit and free intracellular polyamines (PA) to variability of IK1 in the mouse heart. The kinetics of activation was measured in Kir2 concatemeric tetramers with known subunit stoichiometry. Inclusion of only one Kir2.3 subunit to a Kir2.1 channel led to a ~3 fold slowing of activation kinetics, with greater slowing upon subsequent additions of Kir2.3 subunits. Activation kinetics of IK1 in both ventricles and both atria was found to correspond to fast activating Kir2.1/Kir2.2 channels, suggesting no major contribution of Kir2.3 subunits. In contrast, IK1 displayed significant variation in both the current density and inward rectification, suggesting involvement of intracellular PAs. The total levels of PAs were similar across the mouse heart. Measurements of the free intracellular PAs in isolated myocytes using transgenically expressed Kir2.1 channels as PA sensors, revealed microheterogeneity of IK1 rectification in any region of the heart, as well as lower levels of free PAs in atrial myocytes when compared to ventricular cells. These findings provide a quantitative explanation for the regional heterogeneity of IK1.
