PT  - JOURNAL ARTICLE
AU  - Song, Jin-Ho
AU  - Huang, Chao-Sheng
AU  - Nagata, Keiichi
AU  - Yeh, Jay Z.
AU  - Narahashi, Toshio
TI  - Differential Action of Riluzole on Tetrodotoxin-Sensitive and Tetrodotoxin-Resistant Sodium Channels
DP  - 1997 Aug 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 707--714
VI  - 282
IP  - 2
4099  - http://jpet.aspetjournals.org/content/282/2/707.short
4100  - http://jpet.aspetjournals.org/content/282/2/707.full
SO  - J Pharmacol Exp Ther1997 Aug 01; 282
AB  - The effects of riluzole, a neuroprotective drug, on tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistant (TTX-R) sodium channels in rat dorsal root ganglion neurons were studied using the whole-cell patch clamp technique. At the resting potential, riluzole preferentially blocked TTX-S sodium channels, whereas at more negative potentials, it blocked both types of sodium channels almost equally. The apparent dissociation constants for riluzole to block TTX-S and TTX-R sodium channels in their resting state were 90 and 143 μM, respectively. Riluzole shifted the voltage dependence of activation of TTX-R sodium channels in the depolarizing direction more than that of TTX-S sodium channels. The voltage dependence of the fast inactivation of both types of sodium channels was shifted in the hyperpolarizing direction in a dose-dependent manner, and the apparent dissociation constants for riluzole to block the inactivated channels were estimated to be 2 and 3 μM for the TTX-S and TTX-R sodium channels, respectively, indicating a much higher affinity for the inactivated channels than for the resting channels. Riluzole was equally effective in blocking both types of sodium channels in their slow inactivated state. Since more TTX-S channels are inactivated than TTX-R channels at the resting potential, riluzole blocks TTX-S sodium channels more potently than TTX-R sodium channels. It was concluded that one of the mechanisms by which riluzole exerts its neuroprotective action is to preferentially block the inactivated sodium channel of damaged or depolarized neurons under ischemic conditions, thereby suppressing excess stimulation of the glutamatergic receptors and massive influx of Ca++. The American Society for Pharmacology and Experimental Therapeutics