Rol del cotransportador Na+/glucosa 1 (SGLT1) en las arritmias inducidas por incrementos en la glucosa extracelular

ILLANES A,; FEDERICO M,; NUOZZI G, ; LOPEZ S, ; VILLA ABRILLE C,; SAID M, ; PALOMEQUE J

Congreso; International Society for Heart Research (ISHR) Latin American Section,; 2022

The changes in [glucose]e (∆GE) alter the Ca2+i handling, inducing arrhythmogenic events (AE) Ca2+-Calmodulin kinase II (CaMKII) dependent, which activates the Na+-Ca2+exchanger (NCX) in the forward mode. The Na+ entering, would generate ectopic beats and this phenomenon would be favored by the participation of Na+/glucose 1 cotransporter (SGLT1), which is the unique isoform in the heart. In this context, the AE inducing by ∆GE has not been studied, and this is our aim of the following project.We used isolated myocytes loaded with Fura-2-AM, I which we measured Ca2+i by epifluorescence (intracellular Ca2+ transient, CaiT), and perfused whole heart where we measured developed pressure. We use an SGLT inhibitor, phlorozin 10µM. The ∆GE from 5,5mM (low glucose, LG) to 11mM (Normal Glucose, GN) and from GN to 25mM (high glucosa, AG), majorly induced alteration in Ca2+i handling, such us an increase or a decrease of the CaiT. Independently on the effects on CaiT after the ∆GE, we observed AE in a 100% from LG-GN and a 78% from GN-AG. In isolated whole hearts, we observed the same pattern of AE as we observed in isolated myocytes with the ∆GE. When we use phlorozin, the emerge of AE were significant prolonged in both preparations. In conclusion, the acute ∆GE would induce AE dependent on SGLT1activity.