Differential modulation of sodium channel gating and persistent sodium currents by the beta1, beta2, and beta3 subunits.
Brain sodium channels are complexes of a pore-forming alpha subunit with auxiliary beta subunits, which are transmembrane proteins that modulate alpha subunit function. The newly cloned beta3 subunit is shown to be expressed broadly in neurons in the central and peripheral nervous systems, but not in glia and most nonneuronal cells. Beta1, beta2, and beta3 subunits are coexpressed in many neuronal cell types, but are differentially expressed in ventromedial nucleus of the thalamus, brain stem nuclei, cerebellar Purkinje cells, and dorsal root ganglion cells. Coexpression of beta1, beta2, and beta3 subunits with Na(v)1.2a alpha subunits in the tsA-201 subclone of HEK293 cells shifts sodium channel activation and inactivation to more positive membrane potentials. However, beta3 is unique in causing increased persistent sodium currents. Because persistent sodium currents are thought to amplify summation of synaptic inputs, expression of this subunit would increase the excitability of specific groups of neurons to all of their inputs.
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Y
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Department of Pharmacology, University of Washington, Seattle 98195-7280, USA.
Curtis
R
R
Lawson
D
D
Gilbride
K
K
Ge
P
P
DiStefano
P S
PS
Silos-Santiago
I
I
Catterall
W A
WA
Scheuer
T
T
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology / Q000378:metabolism; D008564:Membrane Potentials / Q000502:physiology; D009420:Nervous System / Q000378:metabolism*; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D017933:Peripheral Nervous System / Q000166:cytology / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*
D012333:RNA, Messenger; D015222:Sodium Channels