Omega-conotoxin GVIA potently inhibits the currents mediated by P2X receptors in rat DRG neurons.
We examined effects of omega-conotoxin previously known as a selective blocker of N-type calcium channels, on the adenosine triphosphate (ATP)-induced currents in the rat dorsal root ganglion neurons. These neurons express at least two types of ionotropic purinoreceptors: P2X3 receptors that have very rapid desensitization kinetics and P2X2/X3 heterooligomeric receptor, which exhibits slow desensitization. We have found that omega-conotoxin GVIA potently inhibits the inward currents mediated by both receptor types. This effect was specific for the receptor subtypes: the IC(50) value for responses evoked by 10 microM ATP was 21.2 +/- 1.7 nM for the P2X3 receptor-mediated responses and 3.84 +/- 0.43 microM for slower responses mediated by P2X2/X3 heteropolymers. The efficacy of another type of omega-conotoxin, MVIIC, is much lower: at 10 microM the latter toxin inhibited the rapidly desensitizing response by 65% and the slowly desensitizing response by 18%. The effects of both toxins were reversible and independent on the membrane potential. Omega-Conotoxin GVIA shifted the dose dependence for the agonistic action of ATP on P2X3 receptors to higher concentrations without producing any effect on the kinetics of the response. It is suggested that omega-conotoxin allosterically modulates the receptor properties, rather than competes for the agonist binding site.
Lalo
U V
UV
Department of Cellular Membranology, Bogomoletz Institute of Physiology, Kyiv, Ukraine.
Pankratov
Y V
YV
Arndts
D
D
Krishtal
O A
OA
D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007473:Ion Channels / Q000187:drug effects* / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009475:Neurons, Afferent / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018048:Receptors, Purinergic P2 / Q000187:drug effects* / Q000378:metabolism; D058476:Receptors, Purinergic P2X2; D058477:Receptors, Purinergic P2X3; D020866:omega-Conotoxin GVIA / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D007473:Ion Channels; C546403:P2rx2 protein, rat; C546410:P2rx3 protein, rat; D018048:Receptors, Purinergic P2; D058476:Receptors, Purinergic P2X2; D058477:Receptors, Purinergic P2X3; D000255:Adenosine Triphosphate; D020866:omega-Conotoxin GVIA