Increased mitochondrial free Ca²⁺ during ischemia is suppressed, but not eliminated by, germline deletion of the mitochondrial Ca²⁺ uniporter.

ABSTRACT: Mitochondrial Ca²⁺ overload is proposed to regulate cell death via opening of the mitochondrial permeability transition pore. It is hypothesized that inhibition of the mitochondrial Ca²⁺ uniporter (MCU) will prevent Ca²⁺ accumulation during ischemia/reperfusion and thereby reduce cell death. To address this, we evaluate mitochondrial Ca²⁺ in ex-vivo-perfused hearts from germline MCU-knockout (KO) and wild-type (WT) mice using transmural spectroscopy. Matrix Ca²⁺ levels are measured with a genetically encoded, red fluorescent Ca²⁺ indicator (R-GECO1) using an adeno-associated viral vector (AAV9) for delivery. Due to the pH sensitivity of R-GECO1 and the known fall in pH during ischemia, hearts are glycogen depleted to decreas

SUBMITTER: Petersen CE 

PROVIDER: S-EPMC10529381 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature