SR33805

SR33805 is a potent antagonist of Ca2+ channel (EC50s of 4.1 nM and 33 nM in depolarized and polarized conditions, respectively) Acute treatment with SR33805 restored the MI-altered cell shortening without affecting the Ca (2+) transient amplitude, suggesting an increase of myofilament Ca (2+) sensitivity in MI myocytes. Indeed, a SR33805-induced sensitization of myofilament activation was found to be associated with a slight increase in myosin light chain-2 phosphorylation and a more significant decrease on troponin I (TnI) phosphorylation. Decreased TnI phosphorylation was related to inhibition of protein kinase A activity by SR33805. Finally, administration of a single intra-peritoneal bolus of SR33805 (20 mg/kg) improved end-systolic strain and fractional shortening of MI hearts.