Role of Ca2+ availability to myofilaments and their sensitivity to Ca2+ in myocyte contractile dysfunction in heart failure.
OBJECTIVE
Contractile function is depressed at the isolated myocyte level in heart failure (HF), which could result from the decreased availability of intracellular calcium ([Ca2+]i) to the myofibrils and/or the depressed sensitivity of myofilaments to [Ca2+]i. However, the cellular basis of contractile dysfunction remains unestablished.


METHODS
We isolated left ventricular myocytes from dogs with rapid pacing-induced HF. Cell shortening and [Ca2+]i transients were measured by indo-1 fluorescence and the myofilament Ca2+ sensitivity was analyzed by the shortening-[Ca2+]i relation in intact myocytes as well as by the pCa tension relation in skinned cells.


RESULTS
Peak cell shortening magnitude was depressed in HF, associated with a parallel decrease of [Ca2+]i transient amplitude. There was a significant positive correlation between these two variables (r = 0.71, P < 0.01). In contrast, myofibrillar sensitivity to Ca2+, determined by both intact and skinned myocytes, was comparable between control and HF. Further, there was no significant difference in Ca2+ sensitivity between control and HF even at shorter (1.8 microns) or longer (2.2 microns) sarcomere length.


CONCLUSIONS
Using both intact and skinned cellular preparations, a potential defect in myocyte contractile function in HF was a reduction in Ca2+ availability to the myofilaments, rather than the inherent defects in myofilament sensitivity to Ca2+.
Kinugawa
S
S
Research Institute of Angiocardiology and Cardiovascular Clinic, Kyushu University School of Medicine, Fukuoka, Japan.
Tsutsui
H
H
Satoh
S
S
Takahashi
M
M
Ide
T
T
IgarashiSaito
K
K
Arimura
K
K
Egashira
K
K
Takeshita
A
A
D008841:Actin Cytoskeleton / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D001682:Biological Availability; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D002304:Cardiac Pacing, Artificial; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D004285:Dogs; D006333:Heart Failure / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D018487:Ventricular Dysfunction, Left / Q000378:metabolism*
D015220:Calcium Channels; D002118:Calcium