Aging-associated remodeling of ionic currents in ventricular myocytes of seasonal fish Nothobranchius furzeri

Aging is accompanied by a decline in physiological functions and a plethora of aging-related diseases, with cardiovascular diseases representing the leading cause of morbidity and mortality worldwide. Studying the physiology of cardiac aging in native cardiomyocytes requires relevant model species with a short life cycle. African turquoise killifish (Nothobranchius furzeri), the most short-lived vertebrate, is an emerging model for gerontological experiments. We assessed the effect of aging on major ionic currents and action potential (AP) waveform in working ventricular myocytes of turquoise killifish using whole-cell patch clamp. Aging did not affect either relative heart mass or the size of isolated cardiomyocytes in killifishes. The length of sarcomeres in cardiomyocytes measured after immunocytochemical staining against α-actinin also did not change upon aging. Aging did not affect AP duration and resting membrane potential, but decreased maximum AP upstroke velocity. Fast sodium current I_Na peak amplitude was concordantly reduced in cardiomyocytes from old fishes, underlying remodeling of AP. Aging also caused downregulation of slow delayed rectifier potassium current I_Ks. By comparison, rapid delayed rectifier potassium current, I_Kr, as well as the background inward rectifier current, I_K1, were unaffected. Calcium L- and T-type currents were downregulated in old fishes. Thus, aging is associated with electrophysiological remodeling of fish working ventricular myocardium, which may increase susceptibility to cardiac dysfunction and arrhythmias. Our results support the use of turquoise killifish as a relevant model for studying cardiac aging and highlight its potential as a platform for testing pharmacological interventions targeting age-related cardiac changes.