Circulation, Vol 85, 518-525, Copyright © 1992 by American Heart Association
A D'Agnolo, GB Luciani, A Mazzucco, V Gallucci and G Salviati
BACKGROUND. We performed a comparative study on Ca2+ release activity of
the sarcoplasmic reticulum and calcium sensitivity of contractile apparatus
of chemically skinned myocardial fibers obtained from four nonfailing human
hearts and 13 excised hearts from patients with idiopathic dilated
cardiomyopathy. METHODS AND RESULTS. Ca2+ sensitivity of contractile
apparatus was studied by following the isometric tension developed by
chemically skinned myocardial fibers challenged with solutions of
decreasing pCa. Ca2+ release from sarcoplasmic reticulum was monitored
indirectly by measurement of the isometric tension developed by skinned
fibers challenged with caffeine. We observed no significant difference of
Ca2+ sensitivity and cooperativity between normal myocardium (pCa50 = 6.00
+/- 0.05; Hill coefficient, nHill = 2.07 +/- 0.10) and dilated
cardiomyopathy (pCa50 = 6.03 +/- 0.07; nHill = 2.72 +/- 0.30) when the
fibers were stretched to 130% of the resting length. We also found that
both in normal myocardium and dilated cardiomyopathy, stretching to 150% of
the resting length increased the Ca2+ sensitivity of the contractile
system; pCa50 = 6.21 +/- 0.01 and 6.13 +/- 0.04 in normal and dilated
cardiomyopathy, respectively, whereas in dilated cardiomyopathy there was a
decrease of Hill coefficient with stretching that was not observed in the
control group. The caffeine threshold in idiopathic dilated cardiomyopathy
was markedly increased compared with the control group, 1.94 +/- 0.27
mmol/l and 0.29 +/- 0.04 mmol/l caffeine, respectively, whereas there were
no significant differences in the extent and rate of caffeine-induced Ca2+
release. CONCLUSIONS. These results indicate that in idiopathic dilated
cardiomyopathy there is no alteration of contractile and regulatory
proteins; on the contrary, the gating mechanism of the Ca2+ release channel
of sarcoplasmic reticulum is abnormal, suggesting a possible involvement of
the excitation- contraction coupling in the pathogenesis of this disease.
It should also be taken into account, however, that the increased caffeine
threshold in dilated cardiomyopathy would be a result of the enhanced
resistance to the skinning procedure secondary to the modification of lipid
species and/or content in sarcoplasmic reticulum membrane.
ARTICLES
Contractile properties and Ca2+ release activity of the sarcoplasmic reticulum in dilated cardiomyopathy
Institute of Cardiovascular Surgery, University of Padua, Italy.
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