Phosphodiesterase 8A (PDE8A) regulates excitation-contraction coupling in ventricular myocytes

Enrico Patrucco, Masami Shimizu Albergine, Luis Fernando Santana, Joseph A. Beavo

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

In ventricular myocytes, activation of protein kinase A (PKA) by 3'-5' cyclic adenosine monophosphate (cAMP) increases the force of contraction by increasing L-type Ca2+ channel currents (ICa) and sarcoplasmic reticulum (SR) Ca2+ release during excitation-contraction coupling. Cyclic-nucleotide phosphodiesterases (PDEs) comprise a large family of enzymes whose role in the cell is to regulate the spatial and temporal profile of cAMP signals by controlling the degradation of this second messenger. At present, however, the molecular identity and functional roles of the PDEs expressed in ventricular myocytes are incompletely understood. Here, we tested the hypothesis that PDE8A plays a critical role in the modulation of at least one compartment of cAMP and hence PKA activity during β-adrenergic receptor (βAR) activation in ventricular myocytes. Consistent with this hypothesis, we found that PDE8A transcript and protein are expressed in ventricular myocytes. Our data indicate that evoked [Ca2+]i transients and ICa increased to a much larger extent in PDE8A null (PDE8A-/-) than in wild-type (WT) myocytes during β-adrenergic signaling activation. In addition, Ca2+ spark activity was higher in PDE8A-/- than in WT myocytes. Our data indicate that PDE8A is a novel cardiac PDE that controls one or more pools of cAMP implicated in regulation of Ca2+ movement through cardiomyocyte.

Original languageEnglish (US)
Pages (from-to)330-333
Number of pages4
JournalJournal of Molecular and Cellular Cardiology
Volume49
Issue number2
DOIs
StatePublished - Aug 2010
Externally publishedYes

Keywords

  • Ca sparks
  • Ca transient
  • CAMP
  • EC coupling
  • L-type Ca channels
  • Phosphodiesterase

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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