Increased calcium loading and inotropy without greater cell death in hypoxic rat cardiomyocytes.
To test whether contractile function in "hypoxic" myocytes treated with high glucose (19.5 mM) can be improved by increasing intracellular Ca2+ without accelerating cell contracture or death, we challenged metabolically inhibited, paced myocytes with high extracellular Ca2+ concentration ([Ca2+]o) and measured simultaneously cell shortening and intracellular Ca2+ concentration ([Ca2+]i). NaCN exposure at a physiological [Ca2+]o level (1.2 mM) caused a decline of contractile function to 58 +/- 8% of the pre-NaCN value (P < 0.001) but increased systolic and diastolic [Ca2+]i by 104 +/- 17 and 37 +/- 9% above baseline (P < 0.01), respectively. Consequent doubling of [Ca2+]o to 2.4 mM, in the presence of NaCN, immediately restored contractile function, and twitch amplitude after 18 min was 123 +/- 14% (P < 0.001) of baseline pre-NaCN values, whereas systolic [Ca2+]i increased further to 225 +/- 63% (P < 0.05) and diastolic [Ca2+]i to 73 +/- 16% above baseline (P < 0.01). This marked increase in [Ca2+]i had no deleterious effect on myocyte diastolic function or survival. These results suggest that if adequate metabolic substrate is provided, contractile function in metabolically inhibited, hypoxic myocytes can be restored by increasing [Ca2+]i without causing short-term cell injury.
Kondo
R P
RP
Cardiac Muscle Research Laboratory, Whitaker Cardiovascular Institute, Boston, Massachusetts 02118, USA.
Apstein
C S
CS
Eberli
F R
FR
Tillotson
D L
DL
Suter
T M
TM
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D016923:Cell Death / Q000502:physiology; D005110:Extracellular Space / Q000378:metabolism; D006321:Heart / Q000503:physiopathology*; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology*; D007425:Intracellular Membranes / Q000378:metabolism; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009994:Osmolar Concentration; D051381:Rats; D017208:Rats, Wistar; D012966:Sodium Cyanide / Q000494:pharmacology
D012966:Sodium Cyanide; D002118:Calcium