Н+–Са2+-обмінник у мітохондріях міометрія: модуляція екзо- та ендогенними сполуками

Abstract

The properties of ΔpH-induced Ca2+-transport from isolated rat myometrium mitochondria was investigated. Ca2+-accu- mulation was carried out in the presence of Mg-ATP2- and succinate. Transport of Ca2+ recorded using Ca2+-sensitive fluorescent probe Fluo-4 AM. It is shown that acidification of extramitochondrial medium is accompanied by stimulation of Ca2+ release from mitochondria. This process is insensitive to the tetraphenylphosphonium which is relatively specific Na+-Ca2+-exchanger inhibitor of mitochondrial inner membrane, but inhibited in the presence of monoclonal antibodies directed against the protein LETM1 (Anti-LETM1). LETM1 protein in some tissues is the molecular basis of the H+-Ca2+-exchanger functioning on mitochondria. It was found that the H+-Ca2+-exchanger is stimulated by 100 μM amiloride (diuretic) and inhibited by Mg ions in milimolar concentrations. The transport system was completely resistant to the action of nitric oxide (sodium nitroprusside and sodium nitrite), but was stimulated by macrocyclic compounds of Calixarenes (C-97 and C-99) in submicromolar concentrations. Thus, the mitochondria of rat myometrium probably not have a system of Na+-Ca2+-exchanger, and provide the maintenance of the matrix Ca2+-homeostasis with H+-Ca2+-exchanger. Since the transport system high affinity activated by Calixarenes, further investigation of the influence of these compounds on the transport process makes promising.