okadaic-acid and Hypothyroidism

Conflicting reports exist regarding the influence of beta-adrenergic stimulation on the maximum velocity of shortening (Vmax) in ventricular myocytes. This may be due to an unrecognized effect of maturation. In the present study, the effects of beta-adrenergic receptor stimulation on myocytes from hearts of juvenile nonbred and young adult retired breeder female rats were compared. Ventricular myocytes from young adults had a beta-adrenergic-dependent increase in Vmax and Ca2+-dependent actomyosin ATPase that was not observed in myocytes from juveniles. Myocytes from young adults had both an increase in beta-myosin heavy chain (MHC) and higher basal serine/threonine phosphatase activity compared with juvenile rats. Additional studies established moderate increases in beta-MHC induced by hypothyroidism do not confer myocardial beta-adrenergic responsiveness, whereas inhibition of the higher phosphatase activity in myocytes from young adults blocks the age-dependent, beta-adrenergic-induced increase in cross-bridge cycling rates. We propose that the higher phosphatase activity of myocytes from young adults compared with juveniles allows for a greater functional response of the myocardium to beta-adrenergic stimulation.

Topics: Actin Cytoskeleton; Aging; Animals; Blotting, Western; Bucladesine; Calcium-Transporting ATPases; Enzyme Inhibitors; Female; Heart Ventricles; Hypothyroidism; In Vitro Techniques; Kinetics; Muscle Cells; Myocardial Contraction; Myocardium; Myofibrils; Myosin Heavy Chains; Okadaic Acid; Phosphates; Phosphoric Monoester Hydrolases; Phosphorus Radioisotopes; Phosphorylation; Rats