Phosphorylation of Ser1928 mediates the enhanced activity of the L-type Ca2+ channel Cav1.2 by the β2-adrenergic receptor in neurons

Hai Qian, Tommaso Patriarchi, Jennifer L. Price, Lucas Matt, Boram Lee, Madeline Nieves-Cintrón, Olivia R. Buonarati, Dhrubajyoti Chowdhury, Evanthia Nanou, Matthew A. Nystoriak, William A. Catterall, Montatip Poomvanicha, Franz Hofmann, Manuel F. Navedo, Johannes W. Hell

Research output: Contribution to journalArticlepeer-review

48 Scopus citations


The L-type Ca2+ channel Cav1.2 controls multiple functions throughout the body including heart rate and neuronal excitability. It is a key mediator of fight-or-flight stress responses triggered by a signaling pathway involving b-adrenergic receptors (bARs), cyclic adenosine monophosphate (cAMP), and protein kinase A (PKA). PKA readily phosphorylates Ser1928 in Cav1.2 in vitro and in vivo, including in rodents and humans. However, S1928A knock-in (KI) mice have normal PKA-mediated L-type channel regulation in the heart, indicating that Ser1928 is not required for regulation of cardiac Cav1.2 by PKA in this tissue. We report that augmentation of L-type currents by PKA in neurons was absent in S1928A KI mice. Furthermore, S1928A KI mice failed to induce long-term potentiation in response to prolonged theta-tetanus (PTT-LTP), a form of synaptic plasticity that requires Cav1.2 and enhancement of its activity by the β2-adrenergic receptor (β2AR)-cAMP-PKA cascade. Thus, there is an unexpected dichotomy in the control of Cav1.2 by PKA in cardiomyocytes and hippocampal neurons.

Original languageEnglish (US)
Article numberaaf9659
JournalScience Signaling
Issue number463
StatePublished - Jan 24 2017

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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