Patchliner application note: (0.4 MB)
Cells were kindly provided by Anaxon.
The NaV1.7 gene (SCN9A) encodes a voltage-gated sodium (NaV) channel, primarily expressed in the peripheral nervous system and has been isolated from rat dorsal root ganglion (DRG) neurons, human medullary thyroid cancer cells (hNE-Na) and PC12 cells. Different NaV channels play a key role in modulation of action potentials in the central and peripheral nervous systems. In particular, the fast upstroke of the action potential is mediated by NaV channels.
NaV channels are in part characterized by their TTX-sensitivity (TTX-resistant [TTXr], TTX-sensitive [TTXs]). NaV1.7 is a TTXs channel and is sensitive to TTX in the nanomolar range. The role of hNaV1.7 has yet to be fully elucidated but is proposed to play an important role in nociception and pain sensing. NaV1.7 has been implicated to play a role in disease pain states, in particular inflammatory pain and hypersensitivity to heat following burn injury. Common to many of the voltage-gated ion channels, a number of compounds display a higher affinity for the inactivated state of the channel. For this reason, it is important to be able to reliably measure the effects of compounds at Vhalf of inactivation, the voltage at which 50% of the channels are inactivated. In this Application Note we present data using an 8-channel Patchliner characterizing CHO cells stably expressing hNaV1.7. The hNaV1.7 activation and inactivation properties are consistent with those reported in the literature. The potency of sodium channel blockers mexiletine, tetracaine, amitriptyline and lidocaine were compared using a holding potential of -120 mV vs the Vhalf of inactivation.