Referenced in: none

Automatically associated channels: Nav1.4

Title: Beta1-subunit modulates the Nav1.4 sodium channel by changing the surface charge.

Authors: Loretta Ferrera, Oscar Moran

Journal, date & volume: , 2006 Jun , 172, 139-50

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/16432696

Abstract
Voltage-gated sodium channels, comprised of a pore-forming alpha-subunit and additional regulatory (beta) subunits, play a critical role in regulation of neuronal excitability. Mechanisms of regulation of beta-subunits remain elusive. We have tested the functional effects of beta1 sodium channel subunit on surface charges as a mechanism for channel modulation. HEK-293 cell lines permanently transfected with the sole rat skeletal muscle sodium channel alpha-subunit (Nav1.4), or co-expressing the sodium channel alpha-subunit and beta1-subunit were studied with the whole-cell mode of the patch-clamp technique. At physiological extracellular Ca2+ concentration (2 mM), expression of beta1-subunit did not produce any significant effect on the voltage-dependent properties of sodium currents. However, a shift of half-activation potentials of sodium channel by changing the extracellular Ca2+ was potentiated when beta1 was co-expressed with alpha-subunit. In contrast, the expression of beta1-subunit did not affect the Ca2+ binding to the open or to the closed sodium channel pore, difference of the effect provoked by extracellular Ca2+ could therefore be attributed to an increased in negative surface charge determined by the presence of beta1-subunit. These data are in agreement with the hypothesis of a modulation of the sodium current by the expression of the highly sialylated beta1-subunit, which would alter the channel gating by increasing the density of surface negative charges in the vicinity of the sodium channel voltage sensing machinery.