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Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on April 14, 2005; DOI: 10.1124/jpet.105.084988

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Received for publication February 16, 2005.
Revised April 7, 2005.
Accepted for publication April 8, 2005.

Effects of {alpha}-Dendrotoxin on K+ Currents and Action Potentials in Tetrodotoxin-Resistant Adult Rat Trigeminal Ganglion Neurons

Shinki Yoshida 1* Shigeji Matsumoto 1

1 Nippon Dental University

* Address correspondence to: E-mail: shinki{at}tokyo.ndu.ac.jp

Abstract

To determine whether the {alpha}-dendrotoxin ({alpha}-DTX) sensitive current (a slow inactivating transient current, D-current, ID) contributes to the modification of neuronal function in small-diameter adult rat trigeminal ganglion (TG) neurons insensitive to 1µM tetrodotoxin (TTX), we performed two different types of experiments. In the voltage-clamp mode, two distinct K+ current components, a fast inactivating transient current (IA) and a dominant sustained current (IK), were identified. Alpha-DTX (0.1µM) ranging from 0.001 to 1µM, maximally decreased IA by approximately 20%, and IK by approximately 16% at a +50mV step pulse, and 0.1µM {alpha}-DTX application increased the number of action potentials without changing the resting membrane potential. Irrespective of the absence and presence of 0.1 µM {alpha}-DTX, applications of 4-aminoprydine (4-AP, 0.5mM) and tetraethylammonium (TEA, 2mM) inhibited approximately 50% inhibition of IA and IK, respectively. 4-AP (0.5mM) depolarized the resting membrane potential and increased the number of action potentials in the absence or presence of 0.1µM {alpha}-DTX. TEA prolonged the duration of action potentials in the absence or presence of 0.1 µM {alpha}-DTX. These results suggest that ID contributes to the modification of neuronal function in adult rat TTX-R TG neurons, but that after the loss of ID due to 0.1µM {alpha}-DTX application, 4-AP (0.5mM) and TEA (2mM) still regulate the intrinsic firing properties of the action potential number and shape


Key words: 4-aminoprydine, action potential, alpha-dendrotoxin, tetraethylammonium, tetrodotoxin-resistant neuron, trigeminal ganglion


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