Decreased density of I-to in left ventricular myocytes from German shepherd dogs with inherited arrhythmias

Introduction: A colony of inbred German shepherd dogs with inherited ventricular arrhythmias has been established. Methods and Results: The inward rectifier (I-K1), the slow delayed rectifier (I-Ks), and the transient outward current (I-to) were recorded from epicardial myocytes, and I-to was recorded from Purkinje myocytes isolated from the left ventricles of dogs mildly or severely affected with arrhythmias, and unaffected relatives, There were no differences between unaffected and severely affected dogs in the densities of either I-K1 or I-Ks Peak I-to density at +40 mV was reduced by 49% in epicardial myocytes from severely affected dogs, I-to density was also reduced in a subset of Purkinje myocytes, Boltzmann analysis of steady-state inactivation showed no differences between groups in slope factor, V-1/2, the half-inactivation voltage, was shifted by +6.2 mV in epicardial cells from severely affected versus unaffected dogs, In addition, the time constant for I-to decay was reduced in mildly and severely affected dogs compared to unaffected dogs. Conclusion: Altered density and inactivation of I-to are associated with the presence of severe ventricular arrhythmias in inbred dogs at risk for sudden death.