Related Experiment Video
Updated: Aug 7, 2026
Optical Mapping of Action Potentials and Calcium Transients in the Mouse Heart
Published on: September 13, 2011
Optical mapping of propagation changes induced by elevated extracellular potassium ion concentration in genetically
Bonnie B Punske1, Stefano Rossi, Philip Ershler
1Nora Eccles Harrison Cardiovascular Research and Training Institute, The University of Utah, Salt Lake City, UT 84112-5000, USA. punske@cvrti.utah.edu
Unlabelled:
Diabetes is associated with high rates of cardiovascular disease and sudden death. Therefore, dissecting specific mechanisms, such as the effects of impaired insulin signaling on cardiac electrophysiology may lead to better diagnosis and treatment. Lack of insulin receptors in mouse myocytes has been shown to reduce repolarizing potassium currents and prolong action potential duration. We hypothesized that these changes would manifest as rate-related effects on electrical propagation in the intact heart. This study employed optical mapping to characterize propagation changes in intact mouse hearts with cardiomyocyte-restricted knock out of insulin receptors (CIRKO).
Methods:
Fluorescent signals emitted from excited Di-4-ANEPPS in isolated Langendorff perfused mouse hearts were recorded from the left ventricular epicardium using an 8 by 8 photo diode array. The study included hearts from 8 CIRKO mice and 8 wild type (WT) littermate controls. Hearts were stimulated from the right atrium or the left ventricle at basic cycle lengths ranging from 160 to 280 ms under normal conditions and then after 5 minutes of perfusion with elevated potassium ion concentration (9.4 mM).
Results:
None of the 8 CIRKO hearts maintained regular responses to atrial stimulation at the 160 ms cycle length under normal conditions; however, all of the WT hearts were captured at this rate. Total activation time for a 4 mm by 4 mm area was longer for CIRKO hearts when compared with WT. Average epicardial conduction velocity was slower for the CIRKO when compared to WT. Propagation delay due to the presence of high [K+]e was significant in both CIRKO and WT mice, but significantly longer for the CIRKO hearts.
Conclusions:
These results show that in addition to reducing repolarization currents, impaired myocardial insulin signaling leads to impaired electrical impulse propagation particularly at increased heart rates. These data suggest a link between impaired myocardial insulin signaling and the increased risk of arrhythmia and sudden death in patients with diabetes.
Insights
Impaired insulin signaling in heart cells disrupts electrical signal propagation, especially at higher heart rates. This finding links diabetes to an increased risk of heart arrhythmias and sudden death.
Area of Science:
- Cardiovascular physiology
- Cardiac electrophysiology
- Diabetes research
Background:
- Diabetes is linked to increased cardiovascular disease and sudden death.
- Insulin signaling impacts cardiac function, affecting ion channels and action potential duration.
- Understanding these effects is crucial for improved diagnosis and treatment of diabetic heart complications.
Purpose of the Study:
- To investigate the impact of impaired insulin signaling on cardiac electrical propagation in intact hearts.
- To determine if cardiomyocyte-specific insulin receptor knockout affects heart electrophysiology.
- To explore the relationship between insulin signaling, heart rate, and electrical impulse conduction.
Main Methods:
- Utilized optical mapping with Di-4-ANEPPS in Langendorff-perfused mouse hearts.
- Compared cardiomyocyte-restricted insulin receptor knockout (CIRKO) mice with wild-type (WT) littermates.
- Assessed electrical propagation under varying heart rates and elevated potassium conditions.
Main Results:
- CIRKO hearts showed impaired response to rapid atrial stimulation compared to WT hearts.
- Total activation time was prolonged, and epicardial conduction velocity was slower in CIRKO hearts.
- Propagation delay in response to high extracellular potassium was significantly greater in CIRKO hearts.
Conclusions:
- Impaired myocardial insulin signaling disrupts electrical impulse propagation, particularly at increased heart rates.
- These electrophysiological changes contribute to the elevated risk of arrhythmia and sudden death in diabetic patients.
- Findings highlight a direct link between myocardial insulin resistance and cardiac electrical instability.
