Effects of WIN55,212-2 on voltage-gated sodium channels in trigeminal ganglion neurons of rats.

Objectives: This study was carried out to investigate the effects of WIN55,212-2, a potential cannabinoid receptor agonist, on voltage-gated sodium currents I_Na in cultured trigeminal ganglion neurons of rats, and to investigate whether the anti-nociceptive effects of cannabinoid receptor subtype 1 (CB1) were produced through its modulation on I_Na. Methods: Whole cell patch clamp techniques were used to record I_Na before and after WIN55,212-2 was perfused in cultured trigeminal ganglion neurons of rats. Results: WIN55,212-2 (0.01 μmol/l) could enhance I_Na slightly by 11.5 ± 4.7% (n=7, p<0.05), and this effect could not be blocked by AM251, the CB1 receptor antagonist. However, WIN55,212-2 could inhibit I_Na in concentration dependent manner at concentrations from 0.1 to 100 μmol/l. The inhibitory rates were 17.4 ± 6.0, 22.5 ± 7.8, 43.9 ± 9.4 and 73.9 ± 6.7% respectively by 0.1, 1, 10, 100 μmol/l WIN55,212-2, and the EC₅₀ was 17.8 μmol/l (n=7, p<0.05 or p<0.01). This inhibitory effect could be blocked partly by 1 μmol/l AM251 (n=7, p<0.05). WIN55,212-2 (0.01 μmol/l) shifted the active curve of I_Na leftward slightly (n=7, p<0.05), but had no effect on its stable inactive curve (n=7, p>0.05). WIN55,212-2 (10 μmol/l) did not affect the active and stable inactive curves of I_Na (n=7, p>0.05). Conclusion: WIN55,212-2 had bidirectional (two phases) effects on I_Na in trigeminal ganglion neurons. It might act on different receptors, and the CB1 receptor participated in its modulation on I_Na. [ABSTRACT FROM AUTHOR]