Mitochondrial calcium antagonist receptor (mDHPR)

The mitochondrial calcium antagonist receptor, also known as the mitochondrial dihydropyridine receptor, is a low-affinity, high-capacity binding site for calcium channel blockers (CCBs) located on the inner mitochondrial membrane (IMM). This receptor is specifically characterized by its ability to bind 1,4-dihydropyridines (such as nitrendipine) and benzothiazepines (such as diltiazem), and it is distinct from the high-affinity L-type calcium channels found on the plasma membrane. It is functionally associated with the mitochondrial sodium-calcium exchanger (NCLX, encoded by the SLC24A6 gene) and possibly an inner mitochondrial membrane anion channel, where it plays a critical role in modulating the efflux of calcium from the mitochondrial matrix. By regulating intramitochondrial calcium levels, this receptor indirectly influences the activity of calcium-sensitive matrix dehydrogenases within the tricarboxylic acid (TCA) cycle, thereby modulating mitochondrial bioenergetics and ATP production. It also plays a significant role in determining the threshold for the opening of the mitochondrial permeability transition pore (mPTP), a key event in the initiation of apoptosis and necrotic cell death. Consequently, the mitochondrial calcium antagonist receptor is a target for pharmacological intervention in conditions characterized by mitochondrial calcium overload and oxidative stress, such as myocardial ischemia-reperfusion injury, heart failure, and various neurodegenerative disorders.

Other names

Mitochondrial dihydropyridine receptorMitochondrial nitrendipine binding siteMitochondrial calcium antagonist binding siteLow-affinity mitochondrial dihydropyridine receptor

Inhibition of mitochondrial calcium efflux via the sodium-calcium exchanger (NCLX) or modulation of inner mitochondrial membrane anion channels, leading to the regulation of mitochondrial matrix calcium levels.