Pharmacology and mechanism of action of HSK16149, a selective ligand of α2δ subunit of voltage-gated calcium channel with analgesic activity in animal models of chronic pain

2020 ◽  
pp. JPET-AR-2020-000315
Author(s):  
Xiaoli Gou ◽  
Xiaojuan Yu ◽  
Dongdong Bai ◽  
Bowei Tan ◽  
Pingfeng Cao ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Animal Models ◽  
Calcium Channel ◽  
Analgesic Activity ◽  
Mechanism Of Action ◽  
Voltage Gated ◽  
Selective Ligand ◽  
Α2δ Subunit ◽  
Voltage Gated Calcium Channel

scholarly journals straightjacket is required for the synaptic stabilization of cacophony, a voltage-gated calcium channel α1 subunit

2008 ◽  
Vol 181 (1) ◽  
pp. 157-170 ◽  
Author(s):  
Cindy V. Ly ◽  
Chi-Kuang Yao ◽  
Patrik Verstreken ◽  
Tomoko Ohyama ◽  
Hugo J. Bellen
Keyword(s):  
Calcium Channel ◽  
Neuronal Excitability ◽  
Neuromuscular Junctions ◽  
Synaptic Function ◽  
Voltage Gated ◽  
Α2δ Subunit ◽  
Voltage Gated Calcium Channel ◽  
Α1 Subunit ◽  
Synaptic Level ◽  
Synaptic Stabilization

In a screen to identify genes involved in synaptic function, we isolated mutations in Drosophila melanogaster straightjacket (stj), an α2δ subunit of the voltage-gated calcium channel. stj mutant photoreceptors develop normal synaptic connections but display reduced “on–off” transients in electroretinogram recordings, indicating a failure to evoke postsynaptic responses and, thus, a defect in neurotransmission. stj is expressed in neurons but excluded from glia. Mutants exhibit endogenous seizure-like activity, indicating altered neuronal excitability. However, at the synaptic level, stj larval neuromuscular junctions exhibit approximately fourfold reduction in synaptic release compared with controls stemming from a reduced release probability at these synapses. These defects likely stem from destabilization of Cacophony (Cac), the primary presynaptic α1 subunit in D. melanogaster. Interestingly, neuronal overexpression of cac partially rescues the viability and physiological defects in stj mutants, indicating a role for the α2δ Ca2+ channel subunit in mediating the proper localization of an α1 subunit at synapses.

(l)-Phenylglycine, but not necessarily other α2δ subunit voltage-gated calcium channel ligands, attenuates neuropathic pain in rats

Pain ◽  
2006 ◽  
Vol 125 (1) ◽  
pp. 136-142 ◽  
Author(s):  
James J. Lynch ◽  
Prisca Honore ◽  
David J. Anderson ◽  
William H. Bunnelle ◽  
Kathleen H. Mortell ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Calcium Channel ◽  
Voltage Gated ◽  
Α2δ Subunit ◽  
Voltage Gated Calcium Channel
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