Transient outward current, I-to1, is altered in cardiac memory

Background-Cardiac memory refers to an altered T-wave morphology induced by ventricular pacing or arrhythmias that persist for variable intervals afte r resumption of sinus rhythm. Methods and Results-We induced long-term cardiac memory (LTM) in conscious dogs by pacing the ventricles at 120 bpm for 3 weeks. ECGs were recorded da ily for I hour, during which time pacing was discontinued At terminal study , the heart was removed and the electrophysiology of left ventricular epica rdial myocytes was investigated. Control (C) and LTM ECG did not differ, ex cept for T-wave amplitude, which decreased from 0.12+/-0.18 to -0.34+/-0.21 mV (+/-SEM, P<0.05), and T-wave vector, which shifted from -37+/-12 degree s to -143+/-4 degrees (P<0.05). Epicardial action potentials revealed loss of the notch and lengthening of duration at 20 days (both P<0.05). Calcium- insensitive transient outward current (I-to) was investigated by whole-cell patch clamp. No difference in capacitance was seen in C and LTM myocytes. I-to activated on membrane depolarization to -25+/-1 mV in C and -7+/-1 mV (P<0.05) in LTM myocytes, indicating a positive voltage shift of activation . I-to density was reduced in LTM myocytes, and a decreased mRNA level for Kv4.3 was observed. Recovery of I-to from inactivation was significantly pr olonged: it was 531+/-80 ms (n=10) in LTM and 27+/-6 ms (n=9) in C (P<0.05) at -65 mV. Conclusions-I-to changes an associated with and can provide at least a part ial explanation for action-potential and T-wave changes occurring with LTM.