title: Calcium handling and cell contraction in rat cardiomyocytes depleted of intracellular magnesium.
abstract: OBJECTIVE
  Depressed levels of cardiac Mg have been found in patients with ischaemic heart disease or heart failure, but it is not known whether low intracellular free [Mg2+] ([Mg2+]i) is a causal factor in such myocardial dysfunction. The aims for the present study were to develop a method of lowering [Mg2+]i in myocytes isolated from normal rat hearts, and so to determine whether a low [Mg2+]i itself would cause abnormalities of intracellular Ca2+ ([Ca2+]i) homeostasis or myocyte contractile function in absence of any cardiac disease.
  
  
  METHODS
  Rat ventricular myocytes were loaded with mag-indo-1/AM or indo-1/AM for determination of total [Mg2+]i and [Ca2+]i, respectively. Mitochondrial [Ca2+] was determined by selective loading of indo-1/AM into the mitochondria. Cell contraction was measured using an edge-tracking device. Myocytes were depleted of [Mg2+]i by incubation in absence of external Mg2+. This resulted in a decrease in [Mg2+]i from about 1.3 to 0.3 mM. In subsequent experiments, 1.2 mM MgCl2 was again present in the superfusate.
  
  
  RESULTS
  Under basal conditions (low rate of stimulation, 0.2 Hz, and 1 mM external [Ca2+]), the Mg-depleted cells showed very similar changes in [Ca2+] to control cells, despite an increase in the amplitude of cell contraction. But in presence of high external [Ca2+] (4 mM) and 5 Hz stimulation rate, the Mg-depleted cells showed defects in systolic Ca2+ handling and in cell contraction; in particular, they were unable to increase systolic [Ca2+] in response to the stimulus, unlike control cells. Despite these alterations in total [Ca2+]i, mitochondrial Ca2+ uptake was unchanged in the Mg-depleted cells.
  
  
  CONCLUSIONS
  A low [Mg2+]i can itself cause significant cardiomyocyte dysfunction in absence of any contributing disease state.
authors.affiliation: Bristol Heart Institute, University of Bristol, Bristol, UK. elinor.griffiths@bristol.ac.uk
authors.forename: E J
authors.initials: EJ
authors.lastname: Griffiths
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D048429:Cell Size; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D004558:Electric Stimulation; D007424:Intracellular Fluid / Q000378:metabolism*; D008274:Magnesium / Q000378:metabolism*; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D008274:Magnesium; D002118:Calcium