The α-adrenergic-mediated activation of the cardiac mitochondrial Ca2+ uniporter and its role in the control of intramitochondrial Ca2+in vivo

Abstract

Administration of methoxamine (10 microM, 2 min) to perfused rat hearts increased the rate at which subsequently isolated mitochondria accumulated Ca2+. Methoxamine did not change significantly the development of delta phi with time or the basal rates of Ca2+ flux on inhibition of the uniporter with Ruthenium Red. With 200 microM-Pi, the rates of Ca2+ uptake at constant delta phi were unaffected by the small variations in endogenous [Pi] between mitochondrial preparations, and were also unaffected by changes in internal Ca2+ over the approximate range 8-43 nmol of Ca2+/mg. At low internal Ca2+ (about 8 nmol/mg of protein) the rates of Ca2+ uptake at constant delta phi were unaffected by addition of 200 microM-Pi. Under these conditions, the uniporter activity and the uniporter conductance were increased by 38-40% by methoxamine pretreatment. The endogenous Ca2+ content of mitochondria from control heart was about 1.8 nmol of Ca2+/mg of protein. Perfusion with agonist increased the Ca2+ content as follows: 10 microM-methoxamine (2 min), 48%; 1 microM-isoprenaline (2 min), 100%; 1 microM-adrenaline (2 min), 140%. The implications of the data for the adrenergic control of oxidative metabolism by intramitochondrial Ca2+ is discussed.

Integration of rapid cytosolic Ca2+signals by mitochondria in cat ventricular myocytes

“…P i is the main intracellular membranepermeant anion and enters the mitochondrial matrix together with protons. Mitochondrial P i uptake lowers mitochondrial pH and increases ⌬⌿ and therefore the electrical driving force for Ca 2ϩ uptake (10,40). Thus, through these mechanisms, it is expected that higher levels of P i would facilitate mitochondrial Ca 2ϩ uptake.…”

Rat arterial smooth muscle devoid of ryanodine receptor function: effects on cellular Ca2+ handling

“…Since the Ry receptor and the IP 3 receptor appear to be located to the same stores, or to rapidly communicating stores (Saida & van Breemen, 1984;Komori et al, 1995), Ry treatment will also abolish responses to agents acting through IP 3 . Inhibitors of the Ry receptor, such as ruthenium red, procaine and Mg 2+ all have additional eects on muscle (Crompton et al, 1983;Benham et al, 1985).…”

Inositol hexakisphosphate binding sites in rat heart and brain

“…Functionally, cardiac al-adrenoceptor stimulation has been linked to both InsP6 production (Scholz et al, 1992) and regulation of mitochondrial Ca21 levels (Crompton et al, 1983). Mitochondria contain Fe3", for which InsP6 has extremely high affinity (affinity constant IO' -1O'; Poyner et al, 1993), as a component of the cytochrome system, but it is unclear if this Fe3+ is accessible to InsP6 in binding experiments.…”