| Objectives:Aging is one of the independent risk factors which caused the incidence of atrial fabrillation (AF) increase in the aged, however, the latent electrophysiological mechanisms are still unclear. AF is a common complication observed in patients with hyperthyroidism, and conversely 13% of patients with unexplained AF have high levels of thyroxine. So, in this study, changes of action potential (AP), transient outward potassium current(It0) and ultra-rapid delayed rectifier current(Ikur) of mice atrial myocytes were observed in various age groups, and inspected whether theses characteristics could be induced by thyroxine, furthermore, the electrophysiology mechnisms were investigated underlying the natrual aging.Materials and Methods:Kunming mice were divided into young, middle-aged and old age groups, and hyperthyroidism group. Hyperthyroidism model was established by thyroxine intraperitoneal injection. The atrial cells of each group were isolated respectively into single cell by enzyme hydrolysis on a langendorff apparatus, AP of both the left and right atrial cells, I,o and Ikur of the right cells were recorded by the whole-cell patch clamp technique, and the kinetics of It0 were furtherly analyzed.Results:1. After 3 weeks injection of thyroxine, compared with the control group, the serum T4, T3 of the hyperthyroidism group increased [(45.5±9.5) ng/ml vs (147.5±53.1) ng/ml, P＜0.01; (0.5±0.2) ng/ml vs (3.2±0.9) ng/ml, P＜0.05], and the weight lost [(42.7±1.1) g vs (40.5±0.9) g,P<0.05],and the heart rate speed-up [(486±71) bpmvs (634±91) bpm, P＜0.05].2. Among the young, middle-aged and old age groups, the mean cell membrane capacitance of both left and right atrium cells increased respectively with age. The membrane capacitance of the hyperthyroidism group was higher than the middle age group, but with no significant difference to the old group.3. With age increasing, action potential duration (APD) shortened after the first extension, and there's no significant difference of APD between the hyperthyroidism group and the old group, both were between the young and the middle-aged group's, when near to complete repolarization, the difference of the APD between left and right atrium comes to be significant.4. It0 current density of right atrial myocytes increased with age, half-activation voltage decreased, and half inactivation voltage increased, but the activation curve and inactivation curve in each age group did not change significantly. Compared the IV curve, activation curve and inactivation curve in hyperthyroidism group to the young and middle-aged group, the current density increased, but no change in other aspacts; to the old age-group, there was not significantly different.5. Ikur current density of the right atrial myocytes had no significant difference between the various groups, the Ikur current density of the hyperthyroidism group statistically increased when compared with the other groups.Conclusions:1. This study successfully established hyperthyroidism model mice by thyroxine intraperitoneal injection, which is simple and repeatable.2. AP and the It0 channel of atrial myocytes change with the natural aging or hyperthyroidism, which can lead to increased dispersion of repolarization, conducive to reentry formation and induce arrhythmia.3. Since the atrial Ikur channel becomes stable after birth, there's no age-related changes, however, thyroxine can alter Ikur current density.4. Atrial electrophysiological changes with age, such as the shorten of APD, increase of It0 current density, could be partially induced by thyroxine. |
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