Mitochondrial Calcium Uniporter Complex Activation Protects Against Calcium Alternans in Atrial Myocytes.

Mitochondrial Calcium Uniporter Complex Activation Protects Against Calcium Alternans in Atrial Myocytes. Am J Physiol Heart Circ Physiol. 2020 Aug 28;: Authors: Oropeza-Almazan Y, Blatter LA Abstract Cardiac alternans, defined as beat-to-beat alternations in action potential duration, cytosolic Ca transient (CaT) amplitude and cardiac contraction, is associated with atrial fibrillation (AF) and sudden cardiac death. At the cellular level, cardiac alternans is linked to abnormal intracellular calcium handling during excitation-contraction coupling. We investigated how pharmacological activation or inhibition of cytosolic Ca sequestration via mitochondrial Ca uptake and mitochondrial Ca retention affects the occurrence of pacing-induced CaT alternans in isolated rabbit atrial myocytes.Cytosolic CaTs were recorded using Fluo-4 fluorescence microscopy. Alternans was quantified as the alternans ratio (AR=1-CaTSmall/CaTLarge; CaTSmalland CaTLargeare the amplitudes of the small and large CaTs of a pair of alternating CaTs). Inhibition of mitochondrial Ca sequestration via mitochondrial Ca uniporter complex (MCUC) with Ru360 enhanced the severity of CaT alternans (AR increase) and lowered the pacing frequency threshold for alternans. In contrast, stimulation of MCUC mediated mitochondrial Ca uptake with spermine rescued alternans (AR decrease) and increased the alternans pacing threshold. Direct measurement of mitochondrial [Ca] in membrane...
Source: American Journal of Physiology. Heart and Circulatory Physiology - Category: Physiology Authors: Tags: Am J Physiol Heart Circ Physiol Source Type: research