Sodium channel heterologous expression in mammalian cells and the role of the endogenous β1-subunits

Sodium currents in cell lines transfected with the sole α-subunit, or constitutively expressing sodium channels, have an inactivation that is always prevalently mono-exponential. Differently, expression of α-subunit in Xenopus oocytes exerts slow inactivating currents with biphasic decay, while simultaneous co-transfection of α and β1 restores a mono-exponential (normal) inactivation. A hypothesis for such differences is that an endogenous presence of β1 or β1-alternative splicing, β1A, in cells could account for the normal inactivation. To test this hypothesis and to evaluate the role for the β1A, we inhibited the expression of β1/β1A by antisense oligonucleotides on Nav1.4-transfected human embryonic cell line 293 (HEK) cells. Reduction of β1/β1A produces no significant functional effects in Nav1.4-HEK. This result invalidates the hypothesis that the lack of slow-mode in cell lines is simply due to a constitutive expression of β1/β1A. © 2002 Elsevier Science Ireland Ltd. All rights reserved.