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Accelerated Inactivation of Voltage‐Dependent K + Outward Current in Cardiomyocytes from Thyroid Hormone Receptor α1‐Deficient Mice
Author(s) -
JOHANSSON CATARINA,
KOOPMANN ROLF,
VENNSTRÖM BJÖRN,
BENNDORF KLAUS
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.1540-8167.2002.00044.x
Subject(s) - endocrinology , medicine , depolarization , repolarization , receptor , thyroid , voltage clamp , hormone , patch clamp , biophysics , electrophysiology , biology
Voltage‐Dependent K + Outward Current in TRα1‐Deficient Mice.Introduction: Thyroid hormone affects the electrophysiologic properties of the heart. It is not known which of the different subtypes of thyroid hormone receptors mediate these effects. Methods and Results: Using standard patch‐clamp techniques, we studied time‐ and voltage‐dependent properties of depolarization‐activated K + currents in ventricular heart cells isolated from mice lacking the thyroid hormone receptor α1 (TRα1) and compared these currents with those in respective wild‐type cells. In both groups of cells, the time course of current decay could be described by two inactivating exponential components and a sustained current component. In TRα1‐deficient cells, the total inactivation time course was accelerated due to both increase of the relative contribution of the fast component and shortening of the slow time constant. The peak amplitude of the total current was not altered. The main component of steady‐state inactivation of the voltage‐dependent K + outward current was shifted to more hyperpolarized voltages by 7 mV in TRα1‐deficient cells compared with that in wild‐type cells. Under current‐clamp conditions, action potential duration at 90% repolarization was prolonged in TRα1‐deficient cells compared with that in wild‐type cells by 3.6 msec. Conclusion: The resulting acceleration of the total inactivation time course is proposed to contribute to action potential prolongation and thus to the increased QT end ‐time observed previously on ECG of TRα1‐deficient mice.