Small-molecule Ca_Vα₁⋅Ca_Vβ antagonist suppresses neuronal voltage-gated calcium-channel trafficking.

ABSTRACT: Extracellular calcium flow through neuronal voltage-gated Ca_V2.2 calcium channels converts action potential-encoded information to the release of pronociceptive neurotransmitters in the dorsal horn of the spinal cord, culminating in excitation of the postsynaptic central nociceptive neurons. The Ca_V2.2 channel is composed of a pore-forming α₁ subunit (Ca_Vα₁) that is engaged in protein-protein interactions with auxiliary α₂/δ and β subunits. The high-affinity Ca_V2.2α₁⋅Ca_Vβ₃ protein-protein interaction is essential for proper trafficking of Ca_V2.2 channels to the plasma membrane. Here, structure-based computational screening led to small molecules that disrupt the Ca_V

SUBMITTER: Chen X 

PROVIDER: S-EPMC6233087 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature