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Anchored PKA and regulation of calcium handling in cardiomyocytes
Author(s) -
Jones Brian William,
McKnight G Stanley
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1012.2
Subject(s) - serca , ryanodine receptor , phosphorylation , microbiology and biotechnology , protein kinase a , endoplasmic reticulum , chemistry , calcium , stimulation , biophysics , atpase , biochemistry , biology , enzyme , endocrinology , organic chemistry
Sympathetic stimulation of the heart elevates cAMP levels leading to the rapid phosphorylation of several protein targets by protein kinase A (PKA). Immediate consequences of this phosphorylation include increased Ca 2+ entry through voltage‐gated Ca 2+ channels (Ca V 1.2), Ca 2+ release from sarcoplasmic reticulum (SR) ryanodine receptors, and Ca 2+ reuptake into the SR by the calcium ATPase (SERCA). Enhanced Ca 2+ cycling amplifies the force of contraction and rate of relaxation, substantially improving cardiac performance. Timely and specific phosphorylation of PKA substrates is made possible by scaffolding molecules called A Kinase Anchoring Proteins (AKAPs) which bind directly to PKA, phosphatases, ion channels, and other proteins and membranes to coordinate discrete molecular signaling complexes. Several AKAPs are expressed in the heart. Disruption of all AKAP‐PKA binding abolishes the effect of sympathetic stimulation on Ca 2+ cycling. Our work utilizes AKAP knockout/mutant mice to identify specific AKAP(s) that are essential for Ca V 1.2 and PLB/SERCA regulation. Genetically targeted AKAPs include AKAP7 (15/18), AKAP5 (79/150), and AKAP1.