Dataset Information

The alpha-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.

SUBMITTER: Crompton M

PROVIDER: S-EPMC1152509 | biostudies-other | 1983 Nov

REPOSITORIES: biostudies-other

ACCESS DATA

Similar Datasets

Project description:Mitochondrial Ca(2+) uniporter is the primary influx pathway for Ca(2+) into respiring mitochondria, and hence plays a key role in mitochondrial Ca(2+) homeostasis. Though the mechanism of extra-matrix Ca(2+) dependency of mitochondrial Ca(2+) uptake has been well characterized both experimentally and mathematically, the mechanism of membrane potential (??) dependency of mitochondrial Ca(2+) uptake has not been completely characterized. In this paper, we perform a quantitative reevaluation of a previous biophysical model of mitochondrial Ca(2+) uniporter that characterized the possible mechanism of ?? dependency of mitochondrial Ca(2+) uptake. Based on a model simulation analysis, we show that model predictions with a variant assumption (Case 2: external and internal Ca(2+) binding constants for the uniporter are distinct), that provides the best possible description of the ?? dependency, are highly sensitive to variation in matrix [Ca(2+)], indicating limitations in the variant assumption (Case 2) in providing physiologically plausible description of the observed ?? dependency. This sensitivity is attributed to negative estimate of a biophysical parameter that characterizes binding of internal Ca(2+) to the uniporter. Reparameterization of the model with additional nonnengativity constraints on the biophysical parameters showed that the two variant assumptions (Case 1 and Case 2) are indistinguishable, indicating that the external and internal Ca(2+) binding constants for the uniporter may be equal (Case 1). The model predictions in this case are insensitive to variation in matrix [Ca(2+)] but do not match the ?? dependent data in the domain ???120 mV. To effectively characterize this ?? dependency, we reformulate the ?? dependencies of the rate constants of Ca(2+) translocation via the uniporter by exclusively redefining the biophysical parameters associated with the free-energy barrier of Ca(2+) translocation based on a generalized, non-linear Goldman-Hodgkin-Katz formulation. This alternate uniporter model has all the characteristics of the previous uniporter model and is also able to characterize the possible mechanisms of both the extra-matrix Ca(2+) and ?? dependencies of mitochondrial Ca(2+) uptake. In addition, the model is insensitive to variation in matrix [Ca(2+)], predicting relatively stable physiological operation. The model is critical in developing mechanistic, integrated models of mitochondrial bioenergetics and Ca(2+) handling.

Dataset Information

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets