Effect of amitriptyline on tetrodotoxin-resistant Nav1.9 currents in nociceptive trigeminal neurons.
BACKGROUND
Amitriptyline (AMI) is tricyclic antidepressant that has been widely used to manage various chronic pains such as migraines. Its efficacy is attributed to its blockade of voltage-gated sodium channels (VGSCs). However, the effects of AMI on the tetrodotoxin-resistant (TTX-r) sodium channel Nav1.9 currents have been unclear to present.


RESULTS
Using a whole-cell patch clamp technique, this study showed that AMI efficiently inhibited Nav1.9 currents in a concentration-dependent manner and had an IC50 of 15.16 μM in acute isolated trigeminal ganglion (TG) neurons of the rats. 10 μM AMI significantly shifted the steady-state inactivation of Nav1.9 channels in the hyperpolarizing direction without affecting voltage-dependent activation. Surprisingly, neither 10 nor 50 μM AMI caused a use-dependent blockade of Nav1.9 currents elicited by 60 pulses at 1 Hz.


CONCLUSIONS
These data suggest that AMI is a state-selective blocker of Nav1.9 channels in rat nociceptive trigeminal neurons, which likely contributes to the efficacy of AMI in treating various pains, including migraines.
Department of Neurology, Chinese PLA General Hospital, Beijing 100853, PR China. yushengyuan301@yahoo.com.
Jingyao
J
Liang
Xiaoyan
X
Liu
Jianquan
J
Zheng
Shengyuan
S
Yu
D000639:Amitriptyline / Q000494:pharmacology*; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D062558:NAV1.9 Voltage-Gated Sodium Channel / Q000378:metabolism*; D009619:Nociceptors / Q000187:drug effects* / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D013779:Tetrodotoxin / Q000494:pharmacology*; D012668:Trigeminal Ganglion / Q000187:drug effects* / Q000378:metabolism*
D000779:Anesthetics, Local; D062558:NAV1.9 Voltage-Gated Sodium Channel; C113705:Scn11a protein, rat; D000639:Amitriptyline; D013779:Tetrodotoxin