Article Text

PDF
53 CYTOSOLIC AND MITOCHONDRIAL CALCIUM IN RAT CARDIOMYOCYTES: RESPONSE TO ALDOSTERONISM AND COTREATMENT WITH SPIRONOLACTONE OR AMLODIPINE.
  1. G. Kamalov1,
  2. P. A. Deshmukh1,
  3. S. K. Bhattacharya1,
  4. R. A. Ahokas1,
  5. Y. Sun1,
  6. K. T. Weber1
  1. 1University of Tennessee Health Science Center, Memphis, TN.

Abstract

Purpose An excessive accumulation of intracellular Ca2+ occurs in diverse tissues, including the heart, in rats with aldosterone/salt treatment. This Ca2+ overloading includes total intracellular Ca2+ (both organellar and cytosolic compartments) as well as cytosolic-free [Ca2+]i and mitochondrial-free [Ca2+]m. It may occur as a result of parathyroid hormone receptor-mediated Ca2+ entry as a result of the associated secondary hyperparathyroidism or with aldosterone-mediated increased expression of L-type Ca2+ channels. The distribution of the increased intracellular Ca2+ in aldosteronism that influences mitochondrial and cytosolic compartments remains to be elucidated.

Methods and Results Herein we monitored cytosolic-free Ca2+ in cardiomyocytes harvested from isolated rat hearts perfused with collagenase and intramitochondrial Ca2+ in mitochondria isolated by differential centrifugation. Cells and isolated mitochondria were each loaded with Fura-2, a Ca2+-sensitive probe, with fluorescence monitored by spectrophotometer. The purity of mitochondria was assessed by flow cytometry with mitochondria-specific dye MitoTracker Red. There were four experimental groups: age-/gender-matched controls (C); 4 weeks aldosterone (0.75 μg/h) plus 1% NaCl in drinking water (A); 4 weeks A + spironolactone (S, 150 mg/kg/d by gavage); and 4 weeks A + amlodipine (CCB, 5 mg/kg/d by gavage). We found (p < .05, *A vs C, A + S vs A, A + CCB vs A):

Conclusions Both [Ca2+]m and [Ca2+]i rose in cardiomyocytes harvested from rats with aldosteronism. The rise in [Ca2+]m was concordant with the rise in [Ca2+]i and could be prevented by S but was not altered by CCB cotreatment. The functional significance of these iterations in cardiomyocyte Ca2+ remains to be elucidated and may impact on the redox state of these cells and the electrical behavior of the heart.

Statistics from Altmetric.com

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.