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K K Gunter

Publications and source records attributed to K K Gunter.

28 records · Page 2Linked to original sources
PubMed1983

Mechanism of sodium independent calcium efflux from rat liver mitochondria.

On the basis of primarily two types of observations, it has been suggested that the Na+-independent Ca2+ efflux mechanism of rat liver mitochondria is a passive Ca2+-2H+ exchanger. First, when a pulse of acid is added to a suspension of mitochondria loaded with Ca2+, a pulse of intramitochondrial Ca2+ is often released, even in the presence of the inhibitor of mitochondrial Ca2+ influx, ruthenium red. Second, at a pH near 7, the stoichiometry of Ca2+ released to H+ taken up by Ca2+-loaded mitochondria, following treatment with ruthenium red, has been observed to be 1:2. This evidence for a Ca2+-2H+ exchanger is reexamined here by studying the release of Ca2+ upon acidification of the medium by addition of buffer, the dependence of liver mitochondrial Ca2+ efflux on external medium pH and intramitochondrial pH, and the Ca2+-Ca2+ exchange properties of the Ca2+ efflux mechanism. These studies show no pulse of mitochondrial Ca2+ efflux when pH is abruptly lowered by addition of buffer. The stoichiometry between Ca2+ and H+ fluxes is found to be highly pH dependent. The reported 1:2 stoichiometry between Ca2+ efflux and H+ influx is only observed at one pH. Furthermore, the rate of Ca2+ efflux from mitochondria is found to increase only very slightly at most as suspension pH is decreased. The rate of Ca2+ efflux is not found to increase with increasing intramitochondrial pH. Finally, no Ca2+-Ca2+ isotope exchange can be demonstrated over the Na+-independent efflux mechanism (i.e., in the presence of ruthenium red). It is concluded that these data do not support the hypothesis that the Na+-independent Ca2+ efflux mechanism is a passive Ca2+-2H+ exchanger.

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PubMed1976

Evidence for more than one Ca2+ transport mechanism in mitochondria.

The active transport and internal binding of the Ca2+ analogue Mn2+ by rat liver mitochondria were monitored with electron paramagnetic resonance. The binding of transported Mn2+ depended strongly on internal pH over the range 7.7-8.9. Gradients of free Mn2+ were compared with K+ gradients measured on valinomycin-treated samples. In the steady state, the electrochemical Mn2+ activity was larger outside than inside the mitochondria. The observed gradients of free Mn2+ and of H+ could not be explained by a single "passive" uniport or antiport mechanism of divalent cation transport. This conclusion was further substantiated by observed changes in steady-state Ca2+ and Mn2+ distributions induced by La3+ and ruthenium red. Ruthenium red reduced total Ca2+ or Mn2+ uptake, and both inhibitors caused release of divalent cation from preloaded mitochondria. A model is proposed in which divalent cations are transported by at least two mechanisms: (1) a passive uniport and (2) and active pump, cation antiport or anion symport. The former is more sensitive to La3+ and ruthenium red. Under energized steady-state conditions, the net flux of Ca2+ or Mn2+ is inward over (1) and outward over (2). The need for more than one transport system inregulating cytoplasmic Ca2+ is discussed.

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PubMedDate not supplied

Uptake of calcium by mitochondria: transport and possible function.

Vertebrate mitochondria contain a complex system for transport of Ca2+ and related ions, consisting of two saturable modes of Ca2+ influx and two separate, saturable mechanisms of Ca2+ efflux. The characteristics of the mechanisms of Ca2+ uptake, the uniporter and the RaM, are discussed here and suggestions are made about how the mechanisms may work together and separately to mediate the two physiological roles with which they are most commonly associated-control of the rate of cellular ATP production and induction of the permeability transition and apoptosis. It is argued that more subtlety of control of intramitochondrial free Ca2+ concentration ([Ca2+]m) must be used by the uniporter and the RaM to fulfill their physiological roles than has been commonly recognized. This is because an increase in [Ca2+]m is associated with both increased production of ATP which supports the continued life of the cell and with induction of the permeability transition and possibly apoptosis, which leads to cell death. The saturable mechanisms of mitochondrial Ca2+ efflux and the Ca2+-induced mitochondrial permeability transition, which can transport Ca2+ as well as other ions and molecules and is often considered as a Ca2+ transport mechanism, are being reviewed separately.

Animals↗
PubMedDate not supplied

Release of Ca2+ from mitochondria via the saturable mechanisms and the permeability transition.

The literature, reviewed in the previous article, supports three physiological roles for sequestration of calcium by mitochondria: 1) control of the rate of ATP production, 2) activation of the Ca2+-induced mitochondrial permeability transition (PT), and 3) modulation of cytosolic Ca2+ transients. Removal of Ca2+ from mitochondria permits rapid and efficient changes in the rate of ATP production to adapt to changing demands and can reverse the process of PT induction. Two separate, saturable mechanisms for facilitating Ca2+ efflux from mitochondria exist. In addition, the permeability transition or PT, which may also remove Ca2+ from the mitochondrial matrix, is intimately involved in other important functions such as apoptosis. Here we briefly review what is known about these important mitochondrial mechanisms and from their behavior speculate on their possible and probable functions.

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PubMedDate not supplied

Manganese and calcium transport in mitochondria: implications for manganese toxicity.

Mn2+ is sequestered by liver and brain mitochondria via the mitochondrial Ca2+ uniporter. The mitochondrial Ca2+ uniporter is a cooperative transport mechanism possessing an external activation site and a transport site. Ca2+ binding to the activation site greatly increases the velocity of uptake of both Ca2+ and Mn2+. Electron paramagnetic resonance (EPR) shows that over 97% of the Mn2+ in the mitochondrial matrix is normally bound to the membrane or to matrix proteins. EPR measurements of manganese within living isolated mitochondria can be repeated for hours, and during this time most of the manganese remains in the Mn2+ state. Mn2+ is transported out of mitochondria via the very slow Na(+)-independent efflux mechanism, which is an active (energy-requiring) mechanism. Mn2+ is not significantly transported over the Na(+)-dependent efflux mechanism, which is the dominant efflux mechanism in heart and brain mitochondria. Mn2+ inhibits the efflux of Ca2+ through both of these efflux mechanisms, having an apparent Ki of 7.9 nmol/mg protein on the Na(+)-independent efflux mechanism and an apparent Ki of 5.1 nmol/mg on the Na(+)-dependent efflux mechanism. Mn2+ inhibition of Ca2+ efflux may increase the probability of the mitochondria undergoing the mitochondrial permeability transition (MPT). Intramitochondrial Mn2+ also inhibits State 3 mitochondrial respiration using either succinate or malate plus glutamate as substrate. The data suggest that Mn2+ depletes cellular energy supplies by interfering with oxidative phosphorylation at the level of the F1ATPase and at much higher concentrations, at Complex I. Effects such as these could lead to apoptosis in active neurons.

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