Rapid ventricular repolarization in rodents: electrocardiographic manifestations, molecular mechanisms, and clinical insights.
This article examines specific electrocardiographic (ECG) and electrophysiological features of ventricular repolarization in rats and mice, and the role of depolarization-activated potassium currents in mediating the unique features of ECG recordings in these rodents. This article describes the currents that underlie ventricular repolarization in these rodents, identifies terminology that appropriately describes the unique features of murine ECG recordings, and correlates these unique findings with selected human ECG ventricular repolarization abnormalities. The absence of a distinct isoelectric interval between the QRS complex and the T wave, accompanied by a relatively short QT interval, are common features of ECG recordings in mice and rats, but not in ECGs in guinea pigs. The murine ECG morphology is apparently attributable to the presence of large outward K+ currents that dominate the early phase of ventricular repolarization. In rats and mice, the predominant current underlying the early phase of repolarization appears to be the rapidly activating and inactivating 4-aminopyridine-sensitive transient outward current (ie, I(to)). Importantly, the density of I(to) in rats and mice is high, whereas this current is not evident in the ventricular myocytes of guinea pigs. The high density of I(to) appears to underlie the prominent J wave or downsloping ST-segment elevation seen in rats and mice, whereas the ST-segment is isoelectric in guinea pigs. The unusual J wave and ST-segment pattern in murine ECGs, however, does bear some resemblance to ECG features observed in humans with Brugada syndrome, and with hypothermia and ischemia. These patterns in rats and mice might, therefore, serve as an experimental model for the idiopathic J wave.
Gussak
I
I
Mayo Clinic, Mayo Physician Alliance for Clinical Trials, Rochester, MN 55905, USA. gussak.Ihor@mayo.edu
Chaitman
B R
BR
Kopecky
S L
SL
Nerbonne
J M
JM
D000200:Action Potentials; D000818:Animals; D004562:Electrocardiography; D004594:Electrophysiology; D006168:Guinea Pigs; D006801:Humans; D051379:Mice / Q000502:physiology*; D015221:Potassium Channels / Q000502:physiology; D051381:Rats / Q000502:physiology*; D016276:Ventricular Function
D015221:Potassium Channels