cytochalasin-d and Cardiomegaly

Cardiac hypertrophy in response to systolic pressure loading frequently results in contractile dysfunction of unknown cause. In the present study, pressure loading increased the microtubule component of the cardiac muscle cell cytoskeleton, which was responsible for the cellular contractile dysfunction observed. The linked microtubule and contractile abnormalities were persistent and thus may have significance for the deterioration of initially compensatory cardiac hypertrophy into congestive heart failure.

Topics: Actin Cytoskeleton; Animals; Cardiomegaly; Cats; Colchicine; Cytochalasin D; Desmin; Female; Heart Septal Defects, Atrial; Intermediate Filaments; Male; Microtubules; Myocardial Contraction; Myocardium; Paclitaxel; Pressure; Sarcomeres; Ventricular Function, Right

Mechanical loading of cardiac muscles causes rapid activation of a number of immediate-early (IE) genes and hypertrophy. However, little is known as to how muscle cells sense mechanical load and regulate gene expression. We examined roles of several putative mechanotransducers in stretch-induced hypertrophy of cardiac myocytes grown on a deformable silicone sheet. Using the patch-clamp technique, we found a single class of stretch-activated cation channels which was completely and reversibly blocked by gadolinium. The inhibition of this channel by gadolinium did not affect either stretch-induced expression of the IE genes or hypertrophy. Neither disruption of microtubules with colchicine nor that of actin microfilaments by cytochalasin D prevented the stretch-induced IE gene expression. Arresting contractile activity by tetrodotoxin did not affect the stretch-induced IE gene expression or hypertrophy. These results suggest that stretch-activated cation channels, microtubules, microfilaments, and contractile activity are not the mechanotransducers. Preliminary results suggest that cell stretch may cause a release of a growth factor(s), which in turn initiates a cascade of hypertrophic response of cardiac myocytes.

Topics: Amino Acid Sequence; Animals; Cardiomegaly; Cells, Cultured; Colchicine; Cytochalasin D; Gadolinium; Gene Expression Regulation; Molecular Sequence Data; Myocardial Contraction; Rats; Rats, Wistar; Stress, Mechanical