EFFECTS OF LIDOCAINE AND pH ON THE TETRODOTOXIN-RESISTENT SODIUM CURRENTS FROM RAT TRIGEMINAL ROOT GANGLION NEURONS.
- Author:
Seon Kyung CHO
1
;
Yeo Gab KIM
;
Hyung Chan KIM
Author Information
1. Department of Oral and Maxillofacial Surgery, College of Dentistry, Kyung Hee University, Korea.
- Publication Type:Original Article
- MeSH:
Acidosis;
Analgesia;
Animals;
Ganglion Cysts*;
Hydrogen-Ion Concentration*;
Inflammation;
Lidocaine*;
Neurons*;
Protons;
Rats*;
Sensory Receptor Cells;
Sodium Channels;
Sodium*
- From:Journal of the Korean Association of Oral and Maxillofacial Surgeons
1998;24(3):330-345
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
The extracellular PH has been known to be lowered under the condition of chronic inflammation, and the tetrodotoxin-resistant sodium currents(TTX-r INa ) is thought to responsible for the inflammatory pain. We investigated the effects of PH and lidocaine on the TTX-r INa in sensory neurons derived from abolt rat trigeminal root ganglion(TRG) using whole-cell patch clamp technique to evaluate the underlying mechanisms of the poor analgesia following the administration of local anesthetic solutions into or around the area of the of inflammation. The results are as follows: 1. Two types of INa showing different sensitivity to TTX, TTX-sensitive and TTX-resistant INa , were expressed in the rat TRG neurons. 2. The amplitude and the current-voltage(I-V) relationship of TTX-r INa were significantly affected by the changes of extracellular pH. The acidification of external pH reduced the current amplitude and shifted the I-V relation to the depolarizing directions. 3. The change of extracellular PH also affected the voltage-dependence of activation and steady-state inactivation of TTX-r sodium channels. The voltage-dependence of the channel shifted to a depolarizing direction by the elevated concentration of external hydrogen ion. 4. Lidocaine suppressed TTX-r INa in a dose-dependent manner, and inhibitory effect of lidocaine decresed as the external PH lowered. 5. Lidocaine significantly shifted the activation and steady-state inactivation curves of TTX-r sodium channel to a hyperpolarizing direction by about -20 mV. 6. The effects of lidiocaine on TTX-r sodium channel producing an increase in the probability of channel inactivation greatiy decreased when the external pH was changed to 6.3 or 8.3 7. The 0.1mM lidocaine applied at PH 8.3 shifted the steady-state curve to a hyperpolazizing direction by -20mV compared to that obtained at lidocaine-free pH 7.3 condition. In contrast, the steady-state inactivation curve obtained in the presence of 0.1 mM lidocaine at pH 6.3 614 not showed any significant difference to that obtained at lldocaine-free pH 7.3 condition. These results suggest that the inhibitory action of lidocaine on the TTX-r sodium channel may be derived from the modificition of channel gating as well as blockade of channel pore. The reduced extracellular PH may reduce the TTX-rINa and increase the threshold for activation of TTX-r sodium channels. which may be responsible for the decresed neuronal excitability in the acidified environment. In the presence of lidocaine, however, the sensory neuron is thought to be more excitable in the acidic condition than in physiological PH, which may be due to the decreased lidocaine-induced inactivation of TTX-r sodoum channel as well as reduced amount of hydrophobic neutral from of lidocaine in acidosis.
