Abstract
The deletion mutation of a single lysine residue (ΔK210) in cardiac troponin T is known to cause a form of familial dilated cardiomyopathy CMD1D (OMIM 601494), which is associated with the development of ventricular tachycardia and torsades de pointes that lead to suddern cardiac death. Using a knock-in (KI) mouse model of CMD1D, in which the ΔK210 mutation of cardiac troponin T was incorporated by gene targeting, electrophysiological properties of their ventricular cells were studied using the whole-cell clamp technique under physiological conditions. In the homozygous KI mice, the cells exhibited the action potentials with a plateau phase that had more depolarized peak level and a longer duration than those observed in the cells from wild-type (WT) mice. Also in the KI cells, application of isoproterenol induced early after depolarization and abnormal automaticity, neither of which occured in the WT cells. In the membrane current of the KI cells, peak amplitude of the transient outward K current was smaller, and the inward Na/Ca exchange current associated with the Ca transient was larger than those in the WT cells. On the other hand, no obvious change was observed in the peak amplitude of L-type Ca current. The observed changes in the membrane currents were consistent with the altered action potentialwaveform and the development of the arrhythmogenic afterpotentials in the KI cells. [J Physiol Sci. 2008;58 Suppl:S184]
