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Cytochalasin D reduces Ca 2+ sensitivity and maximum tension via interactions with myofilaments in skinned rat cardiac myocytes
Author(s) -
Calaghan S. C.,
White E.,
Bedut S.,
Guennec J.Y.
Publication year - 2000
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.2000.00405.x
Subject(s) - cytochalasin , cytochalasin d , sarcomere , myofilament , actin , cytoskeleton , cytochalasin b , biophysics , myofibril , myocyte , contractility , tropomyosin , chemistry , biology , microbiology and biotechnology , biochemistry , cell , endocrinology
1 The F‐actin disrupter cytochalasin D depresses cardiac contractility, an effect previously ascribed to the interaction of cytochalasin D with cytoskeletal actin. We have investigated the possibility that this negative inotropic effect is due to the interaction of cytochalasin D with sarcomeric actin of the thin filament. 2 Confocal images of Triton X‐100‐skinned myocytes incubated with a fluorescent conjugate of cytochalasin D revealed a longitudinally striated pattern of binding, consistent with a myofibrillar rather than cytoskeletal structure. 3 Tension‐pCa relationships were determined at sarcomere lengths (SLs) of 2.0 and 2.3 μm following 2 min incubation with 1 μ M cytochalasin D. Cytochalasin D significantly reduced the pCa for half‐maximal activation (pCa 50 ) at both SLs. The shift in pCa 50 was significantly greater at a SL of 2.3 μm compared with that at a SL of 2.0 μm. Cytochalasin D had no effect on the Hill co‐efficient at either SL. 4 Cytochalasin D significantly reduced the maximum tension at both SLs. 5 We suggest that the length‐dependent decrease in myofilament Ca 2+ sensitivity in response to cytochalasin D is due to a decrease in the affinity of troponin C for Ca 2+ . 6 Cytochalasin D has been used for many years as the agent of choice for disruption of cytoskeletal actin. However, we have demonstrated for the first time an interaction of cytochalasin D with sarcomeric actin of the thin filament, which can account for the effects of cytochalasin D on cardiac contractility.