Ca²+/calmodulin-dependent protein kinase II (CaMKII) activity and sinoatrial nodal pacemaker cell energetics.
: Ca(2+)-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 Ca(2+) releases that prompt rhythmic, spontaneous acti...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3581576?pdf=render |
| _version_ | 1818909268656521216 |
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| author | Yael Yaniv Harold A Spurgeon Bruce D Ziman Edward G Lakatta |
| author_facet | Yael Yaniv Harold A Spurgeon Bruce D Ziman Edward G Lakatta |
| author_sort | Yael Yaniv |
| collection | DOAJ |
| description | : Ca(2+)-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 Ca(2+) releases that prompt rhythmic, spontaneous action potentials (APs). This high-throughput signaling consumes ATP.We have previously demonstrated that basal AC-cAMP/PKA signaling directly, and Ca(2+) indirectly, regulate mitochondrial ATP production. While, clearly, Ca(2+)-calmodulin-CaMKII activity regulates ATP consumption, whether it has a role in the control of ATP production is unknown.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 Ca(2+), 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 Ca(2+) 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.CaMKII signaling, a crucial element of normal automaticity in rabbit SANC, is also involved in SANC bioenergetics. |
| first_indexed | 2024-12-19T22:24:13Z |
| format | Article |
| id | doaj.art-83f283c5142440bbba387d25be563df8 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-19T22:24:13Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-83f283c5142440bbba387d25be563df82022-12-21T20:03:34ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0182e5707910.1371/journal.pone.0057079Ca²+/calmodulin-dependent protein kinase II (CaMKII) activity and sinoatrial nodal pacemaker cell energetics.Yael YanivHarold A SpurgeonBruce D ZimanEdward G Lakatta: Ca(2+)-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 Ca(2+) releases that prompt rhythmic, spontaneous action potentials (APs). This high-throughput signaling consumes ATP.We have previously demonstrated that basal AC-cAMP/PKA signaling directly, and Ca(2+) indirectly, regulate mitochondrial ATP production. While, clearly, Ca(2+)-calmodulin-CaMKII activity regulates ATP consumption, whether it has a role in the control of ATP production is unknown.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 Ca(2+), 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 Ca(2+) 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.CaMKII signaling, a crucial element of normal automaticity in rabbit SANC, is also involved in SANC bioenergetics.http://europepmc.org/articles/PMC3581576?pdf=render |
| spellingShingle | Yael Yaniv Harold A Spurgeon Bruce D Ziman Edward G Lakatta Ca²+/calmodulin-dependent protein kinase II (CaMKII) activity and sinoatrial nodal pacemaker cell energetics. PLoS ONE |
| title | Ca²+/calmodulin-dependent protein kinase II (CaMKII) activity and sinoatrial nodal pacemaker cell energetics. |
| title_full | Ca²+/calmodulin-dependent protein kinase II (CaMKII) activity and sinoatrial nodal pacemaker cell energetics. |
| title_fullStr | Ca²+/calmodulin-dependent protein kinase II (CaMKII) activity and sinoatrial nodal pacemaker cell energetics. |
| title_full_unstemmed | Ca²+/calmodulin-dependent protein kinase II (CaMKII) activity and sinoatrial nodal pacemaker cell energetics. |
| title_short | Ca²+/calmodulin-dependent protein kinase II (CaMKII) activity and sinoatrial nodal pacemaker cell energetics. |
| title_sort | ca² calmodulin dependent protein kinase ii camkii activity and sinoatrial nodal pacemaker cell energetics |
| url | http://europepmc.org/articles/PMC3581576?pdf=render |
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