Lidocaine block of neonatal Nav1.3 is differentially modulated by co-expression of beta1 and beta3 subunits

The effects of lidocaine on neonatal Na(v)1.3 (Na(v)1.3n) expressed alone and in combination with beta1 and beta3 subunits in Xenopus oocytes were examined. Lidocaine reversibly inhibited the peak Na(v)1.3n current, shifted the steady-state inactivation curve to hyperpolarized potentials and delayed recovery from inactivation. These effects were attenuated by the co-expression of the beta subunits, with greater attenuating effects being observed in oocytes co-expressing beta1 compared to those co-expressing beta3. Use-dependent block by lidocaine was assessed at 1 Hz train frequency for 60 pulses. Lidocaine caused similar use-dependent block of current amplitude at pulse 60 for Na(v)1.3n and Na(v)1.3n+beta3. In oocytes co-expressing beta1, these use-dependent actions were reduced. In conclusion, the effects of lidocaine on Na(v)1.3n are differentially modulated by beta1 and beta3 subunits. Since these subunits exhibit a complementary distribution, this finding may have importance in our understanding of lidocaine action.