Syntaxin 1A supports voltage-dependent inhibition of alpha1B Ca2+ channels by Gbetagamma in chick sensory neurons.
N-type Ca(2+) channels are modulated by a variety of G-protein-coupled pathways. Some pathways produce a transient, voltage-dependent (VD) inhibition of N channel function and involve direct binding of G-protein subunits; others require the activation of intermediate enzymes and produce a longer-lasting, voltage-independent (VI) form of inhibition. The ratio of VD:VI inhibition differs significantly among cell types, suggesting that the two forms of inhibition play unique physiological roles in the nervous system. In this study, we explored mechanisms capable of altering the balance of VD and VI inhibition in chick dorsal root ganglion neurons. We report that (1) VD:VI inhibition is critically dependent on the Gbetagamma concentration, with VI inhibition dominant at low Gbetagamma concentrations, and (2) syntaxin-1A (but not syntaxin-1B) shifts the ratio in favor of VD inhibition by potentiating the VD effects of Gbetagamma. Variations in expression levels of G-proteins and/or syntaxin provide the means to alter over a wide range both the extent and the rate of Ca(2+) influx through N channels.
Lü
Q
Q
Department of Neuroscience, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
AtKisson
M S
MS
Jarvis
S E
SE
Feng
Z P
ZP
Zamponi
G W
GW
Dunlap
K
K
D017398:Alternative Splicing; D000818:Animals; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D020864:Calcium Channels, N-Type / Q000187:drug effects / Q000378:metabolism*; D002451:Cell Compartmentation; D002478:Cells, Cultured; D002642:Chick Embryo; D017124:Conserved Sequence; D004305:Dose-Response Relationship, Drug; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000235:genetics; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism* / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D009475:Neurons, Afferent / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D021122:Protein Subunits; D051381:Rats; D017386:Sequence Homology, Amino Acid; D050827:Syntaxin 1; D014162:Transfection
D000954:Antigens, Surface; D020864:Calcium Channels, N-Type; C118981:G-protein Beta gamma; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D009419:Nerve Tissue Proteins; D021122:Protein Subunits; C494213:Stx1a protein, rat; D050827:Syntaxin 1; D020962:Heterotrimeric GTP-Binding Proteins; D002118:Calcium