The effect of dibutyryl cAMP on tetrodotoxin-sensitive and -resistant voltage-gated sodium currents in rat dorsal root ganglion neurons and the consequences for their sensitivity to lidocaine

Abstract

Tetrodotoxin-sensitive (TTXS) sodium currents in dorsal root ganglia (DRG) neurons were enhanced by DcAMP applied acutely or by pre-treatment. Pre-treatment increased peak TTXS by 28%. This compared to the increase of tetrodotoxin-resistant sodium currents (TTXR) of 123%. In both cases the increase was associated with a hyperpolarizing shift in activation potentials. Slow inactivation was slower for both TTXR and TTXS in DcAMP treated neurons but rates of recovery from inactivation were not altered. Lidocaine blocked TTX-R with an IC 50 of 0.51 ± 0.15 mM ( n = 9) which was reduced to 0.14 ± 0.05 mM ( n = 8, P < 0.05) in DcAMP treated cells. The sensitivity of TTX-S currents to lidocaine was not altered by DcAMP (control EC 50 = 0.89 ± 0.16 mM, n = 9; DcAMP EC 50 = 0.73 ± 0.19 mM, n = 6). It is concluded that TTXS currents in DRG are, like TTX-R currents, enhanced by cAMP but whilst the pharmacology of TTXR channels with respect to lidocaine is altered, that to TTXS channels is not.