Compensatory role of CaMKII on ICa and SR function during acidosis in rat ventricular myocytes

Pflugers Arch. 2001 Jun;442(3):353-61. doi: 10.1007/s004240100549.

Abstract

It has been suggested that the activity of Ca2+/calmodulin-dependent protein kinase II (CaMKII) increases during acidosis in cardiac muscle. Thus we have investigated the role of CaMKII during acidosis by monitoring intracellular Ca2+ (using fura-2) and ICa (using the perforated patch clamp technique) during acidosis, in the absence and presence of the CaMKII inhibitor KN-93, in rat isolated ventricular myocytes. In the absence of KN-93, acidosis (pH 6.5) increased the amplitude of the fura-2 transient and prolonged its decay, but in the presence of KN-93 acidosis did not alter the amplitude and prolonged the decay more. In the absence of KN-93, acidosis increased the amplitude of the caffeine-induced fura-2 transient but did not alter its amplitude in the presence of KN-93. ICa did not change significantly during acidosis in the absence of KN-93 but decreased during acidosis in the presence of KN-93. These results suggest that activation of CaMKII during acidosis helps to compensate for the direct inhibitory effects of acidosis on sarcoplasmic reticular Ca2+ uptake and ICa.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acidosis / metabolism*
  • Animals
  • Benzylamines / pharmacology
  • Caffeine / pharmacology
  • Calcium / metabolism*
  • Calcium Channels, L-Type / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Enzyme Inhibitors / pharmacology
  • Fluorescent Dyes
  • Fura-2
  • Heart Ventricles / cytology
  • Heart Ventricles / metabolism
  • Hydrogen-Ion Concentration
  • Male
  • Muscle Fibers, Skeletal / metabolism*
  • Myocardium / cytology
  • Myocardium / metabolism*
  • Patch-Clamp Techniques
  • Phosphodiesterase Inhibitors / pharmacology
  • Rats
  • Rats, Wistar
  • Sarcoplasmic Reticulum / metabolism
  • Sulfonamides / pharmacology

Substances

  • Benzylamines
  • Calcium Channels, L-Type
  • Enzyme Inhibitors
  • Fluorescent Dyes
  • Phosphodiesterase Inhibitors
  • Sulfonamides
  • KN 93
  • Caffeine
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Calcium
  • Fura-2