Calcium alternans in myocytes of spontaneously hypertensive rats. Properties and modulation

DI MARZIO G.; MARIANGELO JIE; SOROZA M; GONANO L; MUNDIÑA - WEILENMANN C; SAID M

Mar del Plata

Congreso; Reunión anual de las Sociedades de Biociencia; 2022

SAIC, SAI, SAFIS

Introduction: Cardiac alternans is a dynamical phenomenon which is linked to the genesis of lethal arrhythmias. It has been proposed that alternans is ultimately dependent on alterations in calcium (Ca) cycling dynamics. We demonstrated that the hypertrophied myocardium of the spontaneously hypertensive rats (SHR) shows an increased susceptibility to Ca alternans at early stages of the hypertensive disease. This alternans occurred associated to a lengthened refractoriness of sarcoplasmic reticulum (SR) Ca release and an adverse remodeling of T-tubule network, without alterations in the capacity of SR Ca removal. Objective: To study the subcellular properties of Ca alternans in SHR myocytes and to investigate how extracellular Ca concentration affects Ca alternans. Material and Methods: Frequency-induced Ca alternans was measured in isolated myocytes from 6 and 12 mo-old SHR and compared with age-matched normotensive rats (W). Line scan confocal microscopy was used to examine subcellular Ca dynamics in Fluo-4 loadedmyocytes. Global intracellular Ca transient was measured in Fura-2 loaded myocytes by epifluorescence microscopy. Extracellular Ca was increased from 1 to 2.5 mM. Results: When stimulated at 4 Hz, SHR myocytes exhibited inhomogeneities in the Ca signal with different cell zones alternating out-of-phase. This subcellular alternans, known as discordant alternans, was quantified by the discordance index (DI), standard deviation of local alternans ratio. DI was increased in SHR when compared to aged-matched W myocytes (0.48±0.07 and 0.21±0.02 for SHR and W myocytes respectively, p< 0.05 n= 8-11 myocytes from 3-4 rats). An increase in extracellular Ca from 1 to 2.5 mM, which enhanced Ca transient amplitude and accelerated its decay, alleviated global Ca alternans in SHR myocytes (alternans ratio: 0.50±0.03 and 0.04±0.02 at 1 and 2.5 mM Ca, respectively, p