Calcium handling and cell contraction in rat cardiomyocytes depleted of intracellular magnesium.
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.
Griffiths
E J
EJ
Bristol Heart Institute, University of Bristol, Bristol, UK. elinor.griffiths@bristol.ac.uk
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
D008274:Magnesium; D002118:Calcium