Electrophysiological and pharmacological properties of the human brain type IIA Na+ channel expressed in a stable mammalian cell line.

The human brain voltage-gated Na+ channel type IIA alpha subunit was cloned and stably expressed in Chinese hamster ovary cells and its biophysical and pharmacological properties were studied using whole-cell voltage-clamp. Fast, transient inward currents of up to -8,000 pA were elicited by membrane depolarization of the recombinant cells. Channels activated at -50 mV and reached maximal activation at -10 mV to 0 mV. The reversal potential was 62 +/- 2 mV which is close to the Na+ equilibrium potential. The half-maximal activation and inactivation voltages were -24 +/- 2 mV and -63 +/- 1 mV, respectively. Currents were reversibly blocked by tetrodotoxin with a half-maximal inhibition of 13 nM. The effects of four commonly used anti-convulsant drugs were examined for the first time on the cloned human type IIA channel. Lamotrigine and phenytoin produced concentration- and voltage-dependent inhibition of the type IIA currents, whereas, sodium valproate and gabapentin (up to 1 mM) had no effect. These results indicate that recombinant human type IIA Na+ channels conduct tetrodotoxin-sensitive Na+ currents with similar properties to those observed in recombinant rat brain type IIA and native rat brain Na+ channels. This stable cell line should provide a useful tool for more detailed characterization of therapeutic modulators of human Na+ channels.