title: Mechanotransduction in stretch-induced hypertrophy of cardiac myocytes.
abstract: 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.
authors.affiliation: Indursky Laboratory of Molecular Cardiology, Beth Israel Hospital, Boston, MA.
authors.forename: J
authors.initials: J
authors.lastname: Sadoshima
authors.forename: S
authors.initials: S
authors.lastname: Izumo
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006332:Cardiomegaly / Q000209:etiology / Q000235:genetics / Q000503:physiopathology*; D002478:Cells, Cultured; D003078:Colchicine / Q000494:pharmacology; D015638:Cytochalasin D / Q000494:pharmacology; D005682:Gadolinium / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D008969:Molecular Sequence Data; D009200:Myocardial Contraction / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013314:Stress, Mechanical
chemical_list: D015638:Cytochalasin D; D005682:Gadolinium; D003078:Colchicine