Ca2+/Calmodulin-Dependent Protein Kinase II (CaMKII) Activity and Sinoatrial Nodal Pacemaker Cell Energetics

Yael Yaniv, Harold A. Spurgeon, Bruce D. Ziman, Edward G. Lakatta

Research output: Contribution to journalArticlepeer-review

Abstract

Ca2+-activated basal adenylate cyclase (AC) in rabbit sinoatrial node cells (SANC) guarantees, via basal cAMP/PKA-calmodulin/CaMKII-dependent protein phosphorylation, the occurrence of rhythmic, sarcoplasmic-reticulum generated, sub-membrane Ca2+ releases that prompt rhythmic, spontaneous action potentials (APs). This high-throughput signaling consumes ATP. Aims: We have previously demonstrated that basal AC-cAMP/PKA signaling directly, and Ca2+ indirectly, regulate mitochondrial ATP production. While, clearly, Ca2+-calmodulin-CaMKII activity regulates ATP consumption, whether it has a role in the control of ATP production is unknown. Methods and Results: We superfused single, isolated rabbit SANC at 37°C with physiological saline containing CaMKII inhibitors, (KN-93 or autocamtide-2 Related Inhibitory Peptide (AIP)), or a calmodulin inhibitor (W-7) and measured cytosolic Ca2+, flavoprotein fluorescence and spontaneous AP firing rate. We measured cAMP, ATP and O2 consumption in cell suspensions. Graded reductions in basal CaMKII activity by KN-93 (0.5-3 μmol/L) or AIP (2-10 μmol/L) markedly slow the kinetics of intracellular Ca2+ cycling, decrease the spontaneous AP firing rate, decrease cAMP, and reduce O2 consumption and flavoprotein fluorescence. In this context of graded reductions in ATP demand, however, ATP also becomes depleted, indicating reduced ATP production. Conclusions: CaMKII signaling, a crucial element of normal automaticity in rabbit SANC, is also involved in SANC bioenergetics.

Original languageEnglish (US)
Article numbere57079
JournalPloS one
Volume8
Issue number2
DOIs
StatePublished - Feb 25 2013
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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