Use of the Ca-shortening curve to estimate the myofilament responsiveness to Ca2+ in tetanized rat ventricular myocytes

J Physiol Sci. 2006 Jun;56(3):219-26. doi: 10.2170/physiolsci.RP003706. Epub 2006 Jun 3.

Abstract

We previously estimated the myofilament responsiveness to Ca(2+) in isolated intact ventricular myocytes, using the steady-state relationship between cytosolic Ca(2+) concentration ([Ca(2+)](i)) and cell-shortening during tetanus (Ca-L trajectory). This method was useful and easy; however, it could not be used for a high dose of Ca sensitizer because the instantaneous plots after the application of Ca sensitizer did not make a fixed point of shortening (we used 5% shortening). Therefore we must produce another method to investigate Ca(2+) responsiveness. For an estimation of a wider range of the Ca-L trajectory, we fitted the Ca-L trajectory data with the Hill equation to construct the Ca-shortening curve. To fit this curve, we measured the maximal shortening, which was on average 31.6%. The value of [Ca(2+)](i) to produce the half-maximal shortening (Ca(50)) was dose-dependently decreased by EMD57033 (sensitization). Either isoproterenol or 3-isobutyl-1-methylxanthine increased Ca(50) (desensitization) with a concomitant increase in intracellular c-AMP. EMD57439, a selective PDE-III inhibitor, did not significantly increase the c-AMP concentration and produced little change in Ca(50). These results are in agreement with previous reports with skinned or intact multicellular preparations. The Ca-shortening curve constructed in intact cardiac myocytes can be used to estimate the myofibrillar responsiveness to Ca(2+) in a wide range of [Ca(2+)](i).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-3-isobutylxanthine / pharmacology
  • Actin Cytoskeleton / drug effects
  • Actin Cytoskeleton / physiology*
  • Animals
  • Calcium / pharmacology*
  • Calcium / physiology*
  • Cardiotonic Agents / pharmacology
  • Cell Size / drug effects
  • Cyclic AMP / metabolism
  • Isoproterenol / pharmacology
  • Male
  • Myocardial Contraction / drug effects
  • Myocardial Contraction / physiology
  • Myocytes, Cardiac / cytology
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / physiology*
  • Phosphodiesterase Inhibitors / pharmacology
  • Quinolines / pharmacology
  • Rats
  • Rats, Wistar
  • Tetany
  • Thiadiazines / pharmacology

Substances

  • Cardiotonic Agents
  • Phosphodiesterase Inhibitors
  • Quinolines
  • Thiadiazines
  • EMD 53998
  • Cyclic AMP
  • Isoproterenol
  • Calcium
  • 1-Methyl-3-isobutylxanthine