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  • Pharmacological characterization of recombinant N-type calcium channel (Cav2.2) mediated calcium mobilizytion using FLIPR
    Benjamin, Elfrida R. ...
    The N-type voltage-gated calcium channel (Cav2.2) functions in neurons to regulate neurotransmitter release. It comprises a clinically relevant target for chronic pain. We have validated a calcium ... mobilization approach to assessing Cav2.2 pharmacology in two stable Cav2.2 cell lines: alpha1B, alpha2delta, beta3-HEK-293 and alpha1B, beta3-HEK-293. Cav2.2 channels were opened by addition of KCl and Ca2+ mobilization was measured by Fluo-4 fluorescence on a fluorescence imaging plate reader (FLIPR96). Cav2.2 expression and biophysics were confirmed by patchclamp electrophysiology (EP).Both cell lines responded to KCl with adequate signal-to-background. Signals from both cell lines were inhibited by w-conotoxin (ctx)-MVIIa and w-conotoxin (ctx)-GVIa with IC50 values of 1.8 and 1 nM, respectively, for thethree-subunit stable, and 0.9 and 0.6 nM, respectively, for the two-subunitstable. Other known Cav2.2 blockers were characterized including cadmium, flunarizine, fluspirilene, and mibefradil. IC50 values correlated with literature EP-derived values. Novel Cav2.2 pharmacology was identified inclasses of compounds with other primary pharmacological activities, including Na+ channel inhibitors and antidepressants. Novel Na+ channel compounds with high potency at Cav2.2 were identified in the phenoxyphenyl pyridine, phenoxyphenyl pyrazole, and other classes. The highest potency at Cav2.2 tricyclic antidepressant identified was desipramine.
    Vir: Biochemical pharmacology. - ISSN 0006-2952 (Letn. 72, 2006, str. 770-782)
    Vrsta gradiva - članek, sestavni del
    Leto - 2006
    Jezik - angleški
    COBISS.SI-ID - 22687961

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