Ca²⁺-handling in heart failure – a review focusing on Ca²⁺ sparks

Abstract

[Ca²⁺]_i-transients have been shown to be altered in isolated ventricular myocytes from terminally failing human myocardium. It has been demonstrated that one reason for this alteration is a reduction in the Ca²⁺ content of the sarcoplasmic reticulum (SR). Further investigations were done to investigate, whether there may be an additional defect of the Ca²⁺-release mechanisms from the SR. These release mechanisms were investigated through the recording of Ca²⁺ sparks in single human myocytes. In cardiac myocytes, Ca²⁺ sparks are elementary units of Ca²⁺ release, which occur spontaneously, or which are triggered by Ca²⁺ influx through L-type Ca²⁺-channels (Ca²⁺-induced Ca²⁺ release). Ca²⁺ sparks have been investigated in various animal models of cardiac hypertrophy and cardiac failure and results were conflicting. Discrepancies may be explained by different species and also by the mechanisms underlying hypertrophy and heart failure. This review summarizes our current knowledge on Ca²⁺ sparks in heart failure.