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 v entricular arrhythmias has been established. Methods and Results: The inward rectifier (I-K1), the slow delayed rectifier (I-Ks), and the tr ansient outward current (I-to) were recorded from epicardial myocytes, and I-to was recorded from Purkinje myocytes isolated from the left v entricles of dogs mildly or severely affected with arrhythmias, and un affected relatives, There were no differences between unaffected and s everely affected dogs in the densities of either I-K1 or I-Ks Peak I-t o density at +40 mV was reduced by 49% in epicardial myocytes from sev erely affected dogs, I-to density was also reduced in a subset of Purk inje myocytes, Boltzmann analysis of steady-state inactivation showed no differences between groups in slope factor, V-1/2, the half-inactiv ation voltage, was shifted by +6.2 mV in epicardial cells from severel y affected versus unaffected dogs, In addition, the time constant for I-to decay was reduced in mildly and severely affected dogs compared t o unaffected dogs. Conclusion: Altered density and inactivation of I-t o are associated with the presence of severe ventricular arrhythmias i n inbred dogs at risk for sudden death.