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.
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+/-0.15mM (n=9) which was reduced to 0.14+/-0.05mM (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+/-0.16mM, n=9; DcAMP EC(50)=0.73+/-0.19mM, 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.
Docherty
R J
RJ
King's College London, Wolfson Centre for Age-Related Diseases, Guy's Campus, London Bridge, London SE1 9RT, UK. reginald.docherty@kcl.ac.uk
Farrag
K J
KJ
D000465:Algorithms; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology*; D003627:Data Interpretation, Statistical; D004594:Electrophysiology; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology* / Q000187:drug effects; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects; D007700:Kinetics; D008012:Lidocaine / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D026941:Sodium Channel Blockers / Q000494:pharmacology*; D015222:Sodium Channels / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology*
D000779:Anesthetics, Local; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D013779:Tetrodotoxin; D003994:Bucladesine; D008012:Lidocaine