Role of microtubules in the contractile dysfunction of hypertrophied myocardium
Michael R. Zile, MD, FACC*,
Masaaki Koide, MD*,
Hiroshi Sato, MD*,
Yoshiki Ishiguro, MD ,
Chester H. Conrad, MD, PhD ,
J. Michael Buckley, MS*,
James P. Morgan, MD, PhD, FACC and
George Cooper, IV, MD*
* Cardiology Section of the Department of Medicine and the Department of Physiology, Gazes Cardiac Research Institute, Medical University of South Carolina, and the Veterans Administration Medical Center, Charleston, South Carolina, USA
Veterans Administration Medical Center, Boston, Massachusetts, USA
Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
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Figure 1 Contractions of a normal papillary muscle. Panel A: Shortening extent during an isotonic contraction at baseline. Panel B: Shortening extent during an isotonic contraction after colchicine. Panel C: Active tension during an Lmax isometric contraction at baseline. Panel D: Active tension during an Lmax isometric contraction after colchicine.
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Figure 2 Contractions of a PAB papillary muscle. Panel A: Shortening extent during an isotonic contraction at baseline. Panel B: Shortening extent during an isotonic contraction after colchicine. Panel C: Active tension during an Lmax isometric contraction at baseline. Panel D: Active tension during an Lmax isometric contraction after colchicine.
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Figure 3 Relationship between developed force and muscle length in normal papillary muscles before (closed circles) and after (open circles) colchicine and in PAB papillary muscles before (closed triangles) and after (open triangles) colchicine. *p < 0.05 vs. normal baseline.
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Figure 4 Relationship between shortening extent and force (Panel A) and shortening velocity and force (Panel B) in normal papillary muscles before (closed circles) and after (open circles) colchicine and in PAB papillary muscles before (closed triangles) and after (open triangles) colchicine. *p < 0.5 vs. normal baseline.
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Figure 5 Time-dependent changes in contractile state in normal (circles) and PAB (triangles) papillary muscles. Upper Panel: Active force. Lower Panel: Shortening velocity.
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Figure 6 Time-dependent changes in contractile state in a pair of papillary muscles from a PAB cat. Upper Panel: Active force. Lower Panel: Shortening velocity. Papillary muscle 1 (open triangles) was exposed to colchicine after mechanical performance had reached an equilibrium at 120 min. Papillary muscle 2 (closed triangles) was not exposed to colchicine.
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Figure 7 Time-dependent changes in contractile state in a pair of papillary muscles from a PAB cat. Upper Panel: Active force. Lower Panel: Shortening velocity. Papillary muscle 1 (open triangles) was exposed to colchicine at 210 min, 90 min after it had reached mechanical equilibrium. Papillary muscle 2 (closed triangles) was not exposed to colchicine.
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Figure 8 Time-dependent changes in contractile state in a normal control papillary muscle (circles) and in a normal papillary muscle treated with taxol (triangles). Upper Panel: Active force. Lower Panel: Shortening velocity.
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Figure 9 Immunoblots of normal and PAB papillary muscles. Data are presented in pairs, with free (soluble) ß-tubulin in lane 1 and polymerized ß-tubulin in lane 2 for each pair.
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Figure 10 Immunofluorescence confocal micrographic analysis of microtubules in normal and PAB papillary muscles. Panel A: Normal muscle not exposed to colchicine. Panel B: Normal muscle after colchicine. Panel C: PAB muscle not exposed to colchicine. Panel D: PAB muscle after colchicine. Scale bar = 25 µm.
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Figure 11 Aequorin studies of RV papillary muscle intracellular calcium transients. Upper Panel: Developed tension. Lower Panel: Aequorin calcium light signal. Data were obtained at baseline (solid line) and after treatment with colchicine (dashed line) in muscles from normal and PAB cats.
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