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 annabinoid receptor agonist, on voltage-gated sodium currents I-Na in cultured trtgeminal ganglion neurons of rats, and to investigate whether the anti-nociceptive effects of cannabinoid receptor subtype 1 (CB 1) 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 mu mol/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 CBI receptor antagonist. However, WIN55,212-2 could inhibit I-Na in concentration dependent manner at concentrations from 0.1 to 100 mu mol/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 mu mol/l WIN55,212-2, and the EC50 was 17.8 mu mol/l (n=7, p<0.05 or p<0.01). This inhibitory effect could be blocked partly by 1 mu mol/l AM251 (n=7, p<0.05). WIN55,212-2 (0.01 pmol/l) shifted the active curve of IN., 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 pmol/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 CB 1 receptor participated in its modulation on I-Na.