Age-related functional effects linked to phosphatase activity in ventricular myocytes

Am J Physiol Heart Circ Physiol. 2003 Jul;285(1):H90-6. doi: 10.1152/ajpheart.01018.2002. Epub 2003 Mar 13.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Aging / physiology*
  • Animals
  • Blotting, Western
  • Bucladesine / pharmacology
  • Calcium-Transporting ATPases / antagonists & inhibitors
  • Calcium-Transporting ATPases / metabolism
  • Enzyme Inhibitors
  • Female
  • Heart Ventricles / cytology
  • Heart Ventricles / enzymology
  • Hypothyroidism / enzymology
  • In Vitro Techniques
  • Kinetics
  • Muscle Cells / enzymology*
  • Myocardial Contraction / drug effects
  • Myocardium / cytology
  • Myocardium / enzymology
  • Myofibrils / enzymology
  • Myosin Heavy Chains / metabolism
  • Okadaic Acid / pharmacology
  • Phosphates / metabolism
  • Phosphoric Monoester Hydrolases / metabolism*
  • Phosphorus Radioisotopes
  • Phosphorylation
  • Rats

Substances

  • Enzyme Inhibitors
  • Phosphates
  • Phosphorus Radioisotopes
  • Okadaic Acid
  • Bucladesine
  • Phosphoric Monoester Hydrolases
  • Myosin Heavy Chains
  • Calcium-Transporting ATPases