The mitochondrial calcium uniporter inhibitor Ru265 increases neuronal excitability and reduces neurotransmission via off-target effects.

ABSTRACT:

Background and purpose

Excitotoxicity due to mitochondrial calcium (Ca²⁺) overloading can trigger neuronal cell death in a variety of pathologies. Inhibiting the mitochondrial calcium uniporter (MCU) has been proposed as a therapeutic avenue to prevent calcium overloading. Ru265 (ClRu(NH₃)₄(μ-N)Ru(NH₃)₄Cl]Cl₃) is a cell-permeable inhibitor of the mitochondrial calcium uniporter (MCU) with nanomolar affinity. Ru265 reduces sensorimotor deficits and neuronal death in models of ischemic stroke. However, the therapeutic use of Ru265 is limited by the induction of seizure-like behaviours.

Experimental approach

We examined the effect of Ru265 on synaptic and neuronal function in acute brain slices and hippocampal ne

SUBMITTER: Xu P 

PROVIDER: S-EPMC11309911 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature