α₁-Adrenergic receptor-PKC-Pyk2-Src signaling boosts L-type Ca²⁺ channel Ca_V1.2 activity and long-term potentiation in rodents.

ABSTRACT: The cellular mechanisms mediating norepinephrine (NE) functions in brain to result in behaviors are unknown. We identified the L-type Ca²⁺ channel (LTCC) Ca_V1.2 as a principal target for G_q-coupled α₁-adrenergic receptors (ARs). α₁AR signaling increased LTCC activity in hippocampal neurons. This regulation required protein kinase C (PKC)-mediated activation of the tyrosine kinases Pyk2 and, downstream, Src. Pyk2 and Src were associated with Ca_V1.2. In model neuroendocrine PC12 cells, stimulation of PKC induced tyrosine phosphorylation of Ca_V1.2, a modification abrogated by inhibition of Pyk2 and Src. Upregulation of LTCC activity by α₁AR and formation of a signaling complex with PKC, Pyk2, and Src sugge

SUBMITTER: Man KNM 

PROVIDER: S-EPMC10325713 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature