Abstract

Stoichiometric Phosphorylation of Cardiac Ryanodine Receptor on Serine 2809 by Calmodulin-dependent Kinase II and Protein Kinase A

Highlights

  • A variety of strategies are used by the cell to regulate RYR2 channel activity

  • Li et al [15] found that spark frequency did not increase upon cAMP generation in animals lacking the regulatory protein phospholamban. These data suggest that spark frequency was not dependent upon ryanodine receptor phosphorylation status but dependent upon sarcoplasmic reticulum (SR) Ca2ϩ load, which was most heavily influenced by the phosphorylation status of phospholamban

  • The choice and length of sequence was selected to maximize the importance of the phosphorylation status of Ser-2809, while providing RYR2 flanking sequence to ensure that the antibodies generated were specific for RYR2 protein

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Summary

Introduction

A variety of strategies are used by the cell to regulate RYR2 channel activity. It is anticipated that these regulatory strategies facilitate the fine control of E-C coupling, evidence for this in live cells is rather limited. Phosphorylation of RYR2 by CaMKII or PKA is accompanied by significant changes in channel function in vitro These changes include an increased open probability (Po) [7, 9], the abrogation of the inhibitory effects of CaM [9] and Mg2ϩ [3], heightened channel activity (Po) in response to step changes in Ca2ϩ [13], dissociation of regulatory factors (e.g. FKBP12.6), expression of subconductance states, and the expression of channel activity at diastolic Ca2ϩ concentrations [7]. Despite good evidence of increased channel activity upon RYR2 phosphorylation in vitro, the anticipated manifestation of this is not observed in single cells [15]. We describe the production and characterization of a pair of antisera to the Ser-2809 phosphorylation site of RYR2

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