Jun 29, 2002

The ryanodine receptor modulates the spontaneous beating rate of cardiomyocytes during development

Proceedings of the National Academy of Sciences of the United States of America
Huang-Tian YangKenneth R Boheler


In adult myocardium, the heartbeat originates from the sequential activation of ionic currents in pacemaker cells of the sinoatrial node. Ca(2+) release via the ryanodine receptor (RyR) modulates the rate at which these cells beat. In contrast, the mechanisms that regulate heart rate during early cardiac development are poorly understood. Embryonic stem (ES) cells can differentiate into spontaneously contracting myocytes whose beating rate increases with differentiation time. These cells thus offer an opportunity to determine the mechanisms that regulate heart rate during development. Here we show that the increase in heart rate with differentiation is markedly depressed in ES cell-derived cardiomyocytes with a functional knockout (KO) of the cardiac ryanodine receptor (RyR2). KO myocytes show a slowing of the rate of spontaneous diastolic depolarization and an absence of calcium sparks. The depressed rate of pacemaker potential can be mimicked in wild-type myocytes by ryanodine, and rescued in KO myocytes with herpes simplex virus (HSV)-1 amplicons containing full-length RyR2. We conclude that a functional RyR2 is crucial to the progressive increase in heart rate during differentiation of ES cell-derived cardiomyocytes, consis...Continue Reading

  • References23
  • Citations70


  • References23
  • Citations70


Mentioned in this Paper

Sinoatrial Node
Heart Beat
Shuttle Vectors
Ryanodine Receptor 3
Depressed - Symptom
Muscle Cells
Human herpesvirus 1
Action Potentials

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