Neuron
Volume 19, Issue 2, August 1997, Pages 443-452
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Article
Persistent Sodium Currents through Brain Sodium Channels Induced by G Protein βγ Subunits

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Abstract

Persistent Na+currents are thought to be important for integration of neuronal responses. Here, we show that βγ subunits of G proteins can induce persistent Na+ currents. Coexpression of Gβ2γ3, Gβ1γ3, or Gβ5γ3, but not Gβ1γ1 subunits with rat brain type IIA Na+ channel α subunits in tsA-201 cells greatly enhances a component of Na+ current with a normal voltage dependence of activation but with dramatically slowed and incomplete inactivation and with steady-state inactivation shifted +37 mV. Synthetic peptides containing the proposed Gβγ-binding motif, Gln-X-X-Glu-Arg, from either adenylyl cyclase 2 or the Na+ channel α subunit C-terminal domain reversed the effect of Gβ2γ3 subunits. These results are consistent with direct binding of Gβγ subunits to the C-terminal domain of the Na+ channel, stabilizing a gating mode responsible for slowed and persistent Na+ current. Modulation of Na+ channel gating by Gβγ subunits is expected to have profound effects on neuronal excitability.

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