Influence of intracellular pH on mitochondrial calcium during ischaemia of the isolated rat heart

Abstract

Under physiological conditions cardiac mitochondria seem to play a minor role in maintaining intracellular Ca2+ homoeostasis. However, under conditions of cellular Ca2+ overload, mitochondria may accumulate large amounts of Ca2+. Using transmission and analytical electron microscopy, we investigated, in globally ischaemic rat heart preparations, the influence of intracellular pH on the development of Ca2+-containing intramitochondrial inclusions. We confirmed that under these experimental conditions Ca2+ was a major element of mitochondrial inclusions. The size of these inclusions increased with external Ca2+ concentration. An intracellular alkalinization, produced by addition of 20 mM NH4Cl to the perfusate prior to ischaemia, inhibited the formation of such inclusions. On the other hand, a pre-ischaemic intracellular acidification, produced by the addition and subsequent withdrawal of the 20 mM NH4Cl, increased the number of inclusions present at the end of an ischaemic episode. The presence of amiloride (10(-3) M), prior to and during ischaemia, increased the number of inclusions. These data suggest that cytoplasmic pH may be an important factor in mitochondrial Ca2+ accumulation in pathological conditions.

Heat Stress Contributes to the Enhancement of Cardiac Mitochondrial Complex Activity

“…Myocardial ischemia produces a number of deleterious alterations to the physiological maintenance of intracellular oxygen, calcium, pH, and glucose levels and to osmotic control within cardiomyocytes. [1][2][3] These changes and the increased free radical generation, shown to occur as a consequence of re-oxygenation of the heart, impose both metabolic and oxidative stress. 4,5 This stress is associated with structural damage and mitochondrial dysfunction characterized by the reduced energy production through the oxidative phosphorylation process and loss of respiratory enzyme activity of complexes I-V located in the inner mitochondrial membrane.…”

Mechanisms of calcium buffering in adrenergic neurones and effects of ageing: testing the limits of homeostasis

“…Mitochondria display a robust capacity to sequester small and large calcium loads. Early studies suggested that mitochondria only buffer calcium under non‐physiological conditions, such as when [Ca2+]i exceeds 2 μ m ( Nicholls, 1985), as in some pathological states ( Wilson, Arnold, Burke & Schrier, 1984; Khandoudi, James & Feuvray, 1989). Recently, mitochondria have been established as an important participant in the control of [Ca2+]i transients and have been shown to buffer [Ca2+]i loads within normal physiological ranges and in the absence of pathology ( Werth & Thayer, 1994; Buchholz, Tsai, Foucart & Duckles, 1996; David, Barrett & Barrett, 1998; Pinton et al , 1998 ; Rizzuto et al , 1998 ).…”

Adrenergic nerves compensate for a decline in calcium buffering during ageing

“…In recent years, our understanding of mitochondria as another major component of the calcium‐buffering system has undergone substantial revision. Early studies suggested that mitochondria only buffer calcium under non‐physiological conditions, when [Ca2+]i exceeds 2 μ m ( Nicholls, 1985), or in pathological states ( Wilson, Arnold, Burke & Schrier, 1984; Khandoudi, James & Feuvray, 1989). Recent studies have shown that mitochondria buffer [Ca2+]i loads within normal physiological ranges and in the absence of pathology ( Werth & Thayer, 1994; Buchholz, Tsai, Foucart & Duckles, 1996; David et al , 1998; Rizzuto et al , 1998 ).…”