Dataset Information

Cardiomyocytes from AKAP7 knockout mice respond normally to adrenergic stimulation.

ABSTRACT: Protein kinase A (PKA) is activated during sympathetic stimulation of the heart and phosphorylates key proteins involved in cardiac Ca(2+) handling, including the L-type Ca(2+) channel (Ca(V)1.2) and phospholamban (PLN). This results in acceleration and amplification of the beat-to-beat changes in cytosolic Ca(2+) in cardiomyocytes and, in turn, an increased rate and force of contraction. PKA is held in proximity to its substrates by protein scaffolds called A kinase anchoring proteins (AKAPs). It has been suggested that the short and long isoforms of AKAP7 (also called AKAP15/18) localize PKA in complexes with Ca(V)1.2 and PLN, respectively. We generated an AKAP7 KO mouse in which all isoforms were deleted and tested whether Ca(2+) current, intracellular Ca(2+) concentration, or Ca(2+) reuptake were impaired in isolated adult ventricular cardiomyocytes following stimulation with the ?-adrenergic agonist isoproterenol. KO cardiomyocytes responded normally to adrenergic stimulation, as measured by whole-cell patch clamp or a fluorescent intracellular Ca(2+) indicator. Phosphorylation of Ca(V)1.2 and PLN were also unaffected by genetic deletion of AKAP7. Immunoblot and RT-PCR revealed that only the long isoforms of AKAP7 were detectable in ventricular cardiomyocytes. The results indicate that AKAP7 is not required for regulation of Ca(2+) handling in mouse cardiomyocytes.

SUBMITTER: Jones BW

PROVIDER: S-EPMC3479465 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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Cardiomyocytes from AKAP7 knockout mice respond normally to adrenergic stimulation.

Jones Brian W BW Brunet Sylvain S Gilbert Merle L ML Nichols C Blake CB Su Thomas T Westenbroek Ruth E RE Scott John D JD Catterall William A WA McKnight G Stanley GS

Proceedings of the National Academy of Sciences of the United States of America 20121003 42

Protein kinase A (PKA) is activated during sympathetic stimulation of the heart and phosphorylates key proteins involved in cardiac Ca(2+) handling, including the L-type Ca(2+) channel (Ca(V)1.2) and phospholamban (PLN). This results in acceleration and amplification of the beat-to-beat changes in cytosolic Ca(2+) in cardiomyocytes and, in turn, an increased rate and force of contraction. PKA is held in proximity to its substrates by protein scaffolds called A kinase anchoring proteins (AKAPs). ...[more]

PMID: 23035250

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Dataset Information

Cardiomyocytes from AKAP7 knockout mice respond normally to adrenergic stimulation.

Publications

Cardiomyocytes from AKAP7 knockout mice respond normally to adrenergic stimulation.

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