Ca 2+-overload inhibits the cardiac SR Ca 2+–calmodulin protein kinase activity

Abstract

There is increasing evidence to suggest that Ca 2+–calmodulin dependent protein kinase (CaMK) regulates the sarcoplasmic reticulum (SR) function and thus plays an important role in modulating the cardiac performance. Because intracellular Ca 2+-overload is an important factor underlying cardiac dysfunction in a heart disease, its effect on SR CaMK was examined in the isolated rat heart preparations. Ca 2+-depletion for 5 min followed by Ca 2+-repletion for 30 min, which is known to produce intracellular Ca 2+-overload, was observed to attenuate cardiac function as well as SR Ca 2+-uptake and Ca 2+-release activities. Attenuated SR function in the heart was associated with reduced CaMK phosphorylation of the SR Ca 2+-cycling proteins such as Ca 2+-release channel, Ca 2+-pump ATPase, and phospholamban, decreased CaMK activity, and depressed levels of SR Ca 2+-cycling proteins. These results indicate that alterations in cardiac performance and SR function following the occurrence of intracellular Ca 2+-overload may partly be due to changes in the SR CaMK activity.