Premium
Mathematical Model of the Rapidly Activating Delayed Rectifier Potassium Current I Kr in Rabbit Sinoatrial Node
Author(s) -
OEHMEN CHRISTOPHER S.,
GILES WAYNE R.,
DEMIR SEMAHAT S.
Publication year - 2002
Publication title -
journal of cardiovascular electrophysiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.193
H-Index - 138
eISSN - 1540-8167
pISSN - 1045-3873
DOI - 10.1046/j.1540-8167.2002.01131.x
Subject(s) - diastolic depolarization , repolarization , sinoatrial node , conductance , depolarization , biophysics , medicine , electrophysiology , heart rate , biology , physics , blood pressure , condensed matter physics
Role of I Kr in Rabbit Sinoatrial Node.Introduction: A rapidly activating delayed rectifier potassium current (I Kr ) is known to have an important role in determining the properties of spontaneous pacing in enzymatically isolated rabbit sinoatrial node (SAN) cells. The functional characteristics of I Kr are conferred by its dependence on time, voltage, and external potassium. The aim of this study was to develop a rigorous mathematical representation for I Kr based on experimental findings and to investigate the role of I Kr in the automaticity and intercellular communication of SAN cells. Methods and Results: A Markov model was developed using available experimental data for I Kr in rabbit SAN. The dependence of I Kr on external potassium, [K + ] o , was incorporated using data from both in vitro preparations and results from heterologous expression experiments for this ether‐a‐go‐go related gene product. Our simulation results show the following. (1) I Kr is the dominant repolarizing current in rabbit SAN cells. (2) Deactivation of I Kr contributes to the net current change during the early diastolic depolarization phase. (3) Inward rectification of I Kr results in a decrease in membrane resistance during repolarization relative to plateau. (4) The complex [K + ] o dependence of I Kr confers [K + ] o insensitivity on isolated cells, which may account for the sensitivity of pacing rate to elevated [K + ] o at the tissue level. Conclusion: Model results show that I Kr mediates diastolic depolarization by the kinetics of its decay and by lowering resistance during late repolarization. In elevated [K + ] o , increased chord conductance is balanced by the changes in kinetics and voltage dependence of I Kr so that the pacing rate of single cells may be more [K + ] o insensitive than expected. In addition, elevated [K + ] o increases I Kr magnitude during repolarization but lowers resistance, so current flow through gap junctions is less able to hyperpolarize pacing cells.