Multiple G-Protein βγ Combinations Produce Voltage-Dependent Inhibition of N-Type Calcium Channels in Rat Superior Cervical Ganglion Neurons
By V. Ruiz-Velasco, S. Ikeda. Journal of Neuroscience, 2000
92 citations recorded by the source corpus.
Activation of several G-protein-coupled receptors leads to voltage-dependent (VD) inhibition of N- and P/Q-type Ca2+ channels via G-protein βγ subunits (Gβγ). The purpose of the present study was to determine the ability of different Gβγ combinations to produce VD inhibition of N-type Ca2+ channels in rat superior cervical ganglion neurons. Various Gβγ combinations were heterologously overexpressed by intranuclear microinjection of cDNA and tonic VD Ca2+ channel inhibition evaluated using the whole-cell voltage-clamp technique. Overexpression of Gβ1–Gβ5, in combination with several different Gγ subunits, resulted in tonic VD Ca2+ channel inhibition. Robust Ca2+ channel modulation required coexpression of both Gβ and Gγ. Expression of either subunit alone produced minimal effects. To substantiate the apparent lack of Gβγ specificity, we examined whether heterologously expressed Gβγ displaced native Gβγ from heterotrimeric complexes. To this end, mutant Gβ subunits were constructed that differentially modulated N-type Ca2+ and G-protein-gated inward rectifier K+ channels. Results from these studies indicated that significant displacement does not occur, and thus the observed Gβγ modulation can be attributed directly to the heterologously expressed Gβγ combinations.
Subfields: Cellular and Molecular Neuroscience, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/7cf7cdd00371d7e6606033a9a8183924f126406b
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Citations in the corpus
- Gγ-like (GGL) domains: New frontiers in G-protein signaling and β-propeller scaffolding (2001, background): “Gb5/ Gg2 co-transfection can also cause other Gbg-like effects, such as the modulation of adenylyl cyclase activity [63,64] and the inhibition of N-type calcium channels [ 65 ,66], but cannot activate MAPK/ERK or JNK/SAPK signaling pathways [67] presumably because of an inability to activate PI3Kg [”
- Insights into G protein structure, function, and regulation. (2003, background): “Finally, the rank order for G subtype inhibition of voltage-dependent N-type Ca(2) currents differs from enzyme activation [G 1 G 2 G 5 G 3 G 4; (115)], and this potency difference may be related to the ability of the various G -subunits to physically interact with the LI-II loop of the Ca 2 channel”
- Modulation of glycine-activated ion channel function by G-protein βγ subunits (2003, background): “Results from previous studies in Ca 2+ and GIRK channels predict that the overexpression of Gβγ should tonically modulate the Gly”