Sex and Regional Differences in Left Ventricular Action Potential Duration and Ca2+ Handling: Alterations with Exercise‐training
Authors: Wang Xinrui , Panno Garrett A. , Shields Ryan T. , Fitts Robert H. 
Published: November 2023

Regular exercise‐training is known to reduce the incidences and severity of ischemic heart disease, but the mechanistic nature is unknown. Here we test the hypothesis that one factor of importance is the action potential duration (APD) as it plays a role in controlling intracellular Ca2+ and the incidence of abnormal automaticity. Sprague‐Dawley rats were randomly assigned to voluntary wheel running or control groups. The wheel‐trained females and males ran 16 ± 1 and 11 ± 1 km/day, respectively. After 6–8 weeks, trained (TRN) or sedentary (SED) rats were anesthetized (Nembutal 50 mg/kg body wt), hearts removed and hung on a Langendorff apparatus. The coronary arteries were perfused via the aorta with oxygenated 37° C Krebs‐Henseleit bicarbonate buffer. Monophasic action potentials (MAP) were recorded from the apex and base regions of the left ventricle before and during pacing (400 BPM). Cardiac myocytes were isolated from the same regions with collagenase–protease dispersion technique, and quiescent rod‐shaped myocytes studied. Action potential durations (APD) and intracellular Ca2+ transients were measured simultaneously with high resistance glass micro‐electrode and Fluo‐4AM. The non‐paced apex and base MAP durations were not different between Male (77±5 vs. 76±5) and Female (75±7 vs. 83±4) nor were they significantly altered by wheel running. With pacing, the MAP durations decreased with the greatest change observed in the apex of trained females (84±3 vs. 74±5). Myocyte APD (22° C) showed differences between apex and base at 1 Hz (SED Male: 57±2 vs. 70±2 ms; SED Female: 55±1 vs. 76±2 ms; TRN Male: 65±1 vs. 85±2 ms, TRN Female: 65±1 vs. 88±2 ms) and 10 Hz (SED Male: 42±1 vs. 53±2 ms; SED Female: 35±1 vs. 54±1 ms; TRN Male: 33±1 vs. 50±2 ms, TRN Female: 32±2 vs. 45±1 ms). APD in Myocytes from exercise‐trained compared to sedentary rats were significantly prolonged at 1 Hz. At 10 Hz, APD was shortened more in Myocytes from exercise‐trained compared to sedentary rats in both apex (Male: 33±1 vs. 42±1 ms; Female: 32±2 vs. 35±1 ms) and base (Male: 50±2 vs. 53±2 ms; Female: 45±1 vs. 54±1 ms). At 37°C, myocyte APD's were reduced in all groups, with training effect still apparent. The Ca2+ transient duration mirrored the changes observed in APD with training prolonging the transient at 1 Hz (Male apex: 452±13 vs. 507±13 ms; Female apex: 454±9 vs. 503±9 ms; Male base: 549±12 vs. 608±11 ms; Female base: 583±8 vs. 617±12 ms) while shortening it at 10 Hz(Male apex: 335±15 vs. 285±9 ms; Female apex: 301±9 vs. 283±8 ms; Male base: 410±11 vs. 383±10 ms; Female base: 427±13 vs. 357±10 ms). In conclusion, in both male and female rats, regular exercise‐training prolonged the left ventricle and myocyte APD and Ca2+ transient at low heart rates, while shortening both at high rates. These adaptation will allow increased Ca2+‐induced contractility at rest, while protecting against Ca2+ overload at high work rates or stress conditions.