Ca2+ handling and myofibrillar Ca2+ sensitivity in ferret cardiac myocytes with pressure-overload hypertrophy.
Experiments were performed in aequorin-loaded left ventricular myocytes isolated from hypertrophied hearts and age-matched controls. Five to six months after postvalvular aortic banding, left ventricular hypertrophy was present, as indicated by a 97% (P < 0.001) increase in the left ventricular weight-to-body weight ratio and a 24% (P < 0.001) increase in cell width. In comparison with controls, the hypertrophied myocytes demonstrated that 1) contraction duration was prolonged by 37% (P < 0.001) and was associated with a 44% (P < 0.001) prolongation of the intracellular Ca2+ transient; 2) peak systolic shortening was decreased by 31% (P < 0.001) and was associated with a 21% (P < 0.001) decrease in peak systolic intracellular Ca2+ concentration; 3) both the peak systolic intracellular Ca2+ concentration-to-peak shortening relationship and the intracellular Ca2+ concentration-to-cell shortening relationship at the time of the peak twitch were shifted downward, suggesting a decrease in myofilament Ca2+ responsiveness; and 4) isoproterenol (5 x 10(-8) M) produced equal increases in the peak systolic intracellular Ca2+ of control and hypertrophied myocytes (88 vs. 90%; P > 0.05) in contrast to much smaller increases in the peak cell shortening (170 vs. 73%; P < 0.02) of the hypertrophied myocytes, suggesting a decrease in myofilament Ca2+ responsiveness. These data demonstrate that the hypertrophy-related abnormalities in intracellular Ca2+ handling and mechanical function, previously reported in aequorin-loaded multicellular muscle preparations, are present in isolated myocytes, arguing against changes in the interstitium as essential causative factors.
Wang
J
J
Charles A. Dana Research Institute, Boston, Massachusetts.
Flemal
K
K
Qiu
Z
Z
Ablin
L
L
Grossman
W
W
Morgan
J P
JP
D000331:Aequorin; D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000502:physiology; D006332:Cardiomegaly / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology*; D002469:Cell Separation; D005289:Ferrets; D006973:Hypertension / Q000150:complications*; D007425:Intracellular Membranes / Q000378:metabolism; D008297:Male; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009210:Myofibrils / Q000502:physiology*
D000331:Aequorin; D002118:Calcium