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.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
