Depressed intracellular calcium transients and contraction in myocytes from hypertrophied and failing guinea pig hearts.
We investigated the basis for impaired left ventricular function of hearts in which hypertrophy was produced by gradual pressure overload. We measured myoplasmic free calcium concentration ([Ca2+]i) with fura-2 and sarcomere shortening in single myocytes isolated from control hearts and hypertrophied failing hearts. Diastolic [Ca2+]i was normal, but [Ca2+]i at the peak of contraction was depressed in myocytes from failing hypertrophied hearts. Increasing drive rate from 0.20 Hz to 5.00 Hz increased both diastolic and peak [Ca2+]i. Norepinephrine (3 x 10(-6) M) increased diastolic [Ca2+]i in all cells and tended to normalize peak [Ca2+]i in myocytes from hypertrophied failing hearts during 5.00 Hz drive. Depressed peak [Ca2+]i in the hypertrophied cells was paralleled by significant decreases in both the velocity and percent of sarcomere shortening, which were measured in cells not loaded with fura-2. Sarcomere length was correlated with estimates of [Ca2+]i in intact cells and with controlled levels of [Ca2+] in chemically "skinned" myocytes. A plot of sarcomere length against [Ca2+] gave a single continuous relationship that spanned resting and peak values at all drive rates in both the control and hypertrophied myocytes. Thus heart failure in this model is reflected in impaired myocyte contraction, which is closely related to reduced levels of [Ca2+]i during systole rather than to depressed myofilament sensitivity to Ca2+.
Siri
F M
FM
Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461.
Krueger
J
J
Nordin
C
C
Ming
Z
Z
Aronson
R S
RS
D000818:Animals; D001835:Body Weight; D002118:Calcium / Q000494:pharmacology / Q000502:physiology*; D002303:Cardiac Output, Low / Q000378:metabolism*; D006332:Cardiomegaly / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism; D016257:Fura-2; D006168:Guinea Pigs; D007425:Intracellular Membranes / Q000378:metabolism*; D008297:Male; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009638:Norepinephrine / Q000494:pharmacology; D009929:Organ Size; D012518:Sarcomeres / Q000187:drug effects / Q000502:physiology; D013599:Systole
D002118:Calcium; D016257:Fura-2; D009638:Norepinephrine