title: Sarcomere length-tension relationship of rat cardiac myocytes at lengths greater than optimum.
abstract: The study was aimed at determining both passive and Ca(2+)-activated forces of single skinned rat cardiac cells. Particular attention was paid to the descending limb of the active length-tension curve while the sarcomeric order of stretched cells was investigated before and during contraction. To analyse sarcomere length and sarcomere-length inhomogeneity, a fast Fourier transform (FFT) was employed. The fundamental frequency in the FFT spectrum is a measure of sarcomere length. The full-width-half-maximum of the first-order line is a measure of sarcomere-length inhomogeneity. In relaxing buffer, the sarcomere-length inhomogeneity of skinned cells increased linearly with mean sarcomere length. Upon Ca(2+)-dependent activation of skinned cells contracting isometrically, mean sarcomere length decreased slightly and inhomogeneity increased; both effects were greater at higher Ca(2+)concentrations. Maximum activation was reached at sarcomere lengths between 2.2 and 2.4 microm, whereas the descending limb of the active length-tension curve approached zero force already at approximately 2.8 microm. This steep force decline could not be explained by overly inhomogeneous sarcomere lengths in very long, contracting cells. Rather, the results of mechanical measurements on single cardiac myofibrils implied that high stretching is accompanied by irreversible structural alterations within cardiac sarcomeres, most likely thick-filament disarray and disruption of binding sites between myosin and titin due to changes in titin's tertiary structure. Loss of a regular thick-filament organization may then impair active force generation. We conclude that the descending limb of the cardiac length-tension curve is determined both by the degree of actin-myosin overlap and by the intrinsic properties of titin filaments.
authors.affiliation: Julius Bernstein Institute of Physiology, Martin Luther University Halle-Wittenberg, Halle, D-06097, Germany.
authors.forename: W K
authors.initials: WK
authors.lastname: Weiwad
authors.forename: W A
authors.initials: WA
authors.lastname: Linke
authors.forename: M H
authors.initials: MH
authors.lastname: Wussling
mesh_terms: D008841:Actin Cytoskeleton / Q000648:ultrastructure; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D020013:Calcium Signaling; D064211:Connectin; D009124:Muscle Proteins / Q000737:chemistry; D009200:Myocardial Contraction / Q000187:drug effects; D011494:Protein Kinases / Q000737:chemistry; D017434:Protein Structure, Tertiary; D051381:Rats; D017208:Rats, Wistar; D012518:Sarcomeres / Q000502:physiology* / Q000648:ultrastructure; D013314:Stress, Mechanical
chemical_list: D064211:Connectin; D009124:Muscle Proteins; D011494:Protein Kinases; D002118:Calcium