Monophasic action potential recordings from intact mouse heart: validation, regional heterogeneity, and relation to refractoriness.
BACKGROUND
The monophasic action potential (MAP) technique has been validated in humans and larger animals, but, in mice, MAP recordings available to date show little resemblance to the murine ventricular transmembrane action potential (TAP) measured by conventional microelectrodes. We developed a miniaturized MAP contact electrode technique to establish in isolated mouse hearts: (1) optimal electrode size; (2) validation against TAP; (3) relationship between repolarization and refractoriness; and (4) regional repolarization differences.


RESULTS
In 30 Langendorff-perfused mouse hearts, MAP electrodes of tip diameter 1.5, 1.0, and 0.25 mm were tested by comparing MAPs and TAPs from epicardial and endocardial surfaces of both ventricles. Only the MAP contact electrode of 0.25-mm tip diameter consistently produced MAP recordings that had wave shapes nearly identical to TAP recordings. MAP durations measured at 30%, 50%, 70%, and 90% repolarization (APD30, APD50, APD70, APD90) highly correlated with TAP measurements (r = 0.97, P < 0.00001). APD50 was significantly longer in endocardial than in epicardial recordings (right ventricle: 9.3+/-1.1 msec vs 3.9+/-1.1 msec; left ventricle: 9.9+/-2.1 msec vs 6.2+/-1.9 msec; both P < 0.001), demonstrating transmural repolarization differences. Effective refractory period (ERP) determined at basic cycle lengths from 70 to 200 msec correlated with 80%+/-6% of total repolarization, with an ERP/APD90 ratio of 0.85+/-0.14.


CONCLUSIONS
Murine myocardial repolarization, regional repolarization heterogeneity, and relation to refractoriness can be assessed reliably by this miniaturized MAP contact electrode technique, which renders action potential wave shapes similar to that of intracellular microelectrodes. This technique may be useful for exploring repolarization abnormalities in genetically altered mice.
Knollmann
B C
BC
Clinical Pharmacology and Cardiology Division, Georgetown University Medical Center, Washington, DC 20422, USA.
Katchman
A N
AN
Franz
M R
MR
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D004562:Electrocardiography; D004567:Electrodes, Implanted; D004867:Equipment Design; D006321:Heart / Q000502:physiology*; D006329:Heart Conduction System / Q000502:physiology; D006339:Heart Rate / Q000502:physiology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D023421:Models, Animal; D008955:Models, Cardiovascular; D009200:Myocardial Contraction / Q000502:physiology; D012032:Refractory Period, Electrophysiological / Q000502:physiology; D015203:Reproducibility of Results; D013223:Statistics as Topic; D013997:Time Factors