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This Article Full Text Full Text (PDF) Supplemental Materials All Versions of this Article: 293/6/H3558    most recent 00419.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Panama, B. K. Articles by Lopatin, A. N. Search for Related Content PubMed PubMed Citation Articles by Panama, B. K. Articles by Lopatin, A. N.

Heterogeneity of I_K1 in the mouse heart

Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan

Submitted 4 April 2007 ; accepted in final form 20 September 2007

Previous studies have shown that cardiac inward rectifier potassium current (I_K1) channels are heteromers of distinct Kir2 subunits and suggested that species- and tissue-dependent expression of these subunits may underlie variability of I_K1. In this study, we investigated the contribution of the slowly activating Kir2.3 subunit and free intracellular polyamines (PAs) to variability of I_K1 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 an approximate threefold slowing of activation kinetics, with greater slowing on subsequent additions of Kir2.3 subunits. Activation kinetics of I_K1 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, I_K1 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 I_K1 rectification as well as lower levels of free PAs in atrial myocytes compared with ventricular cells. These findings provide a quantitative explanation for the regional heterogeneity of I_K1.

inward rectifier potassium current; polyamines; transgenic mice; Kir2 channels