P. Kammermeier, V. Ruiz-Velasco, S. Ikeda
Aug 1, 2000
Citations
5
Influential Citations
81
Citations
Quality indicators
Journal
The Journal of Neuroscience
Abstract
Calcium current modulation by the muscarinic cholinergic agonist oxotremorine methiodide (oxo-M) was examined in sympathetic neurons from the superior cervical ganglion of the rat. Oxo-M strongly inhibited calcium currents via voltage-dependent (VD) and voltage-independent (VI) pathways. These pathways could be separated with the use of the specific M1 acetylcholine receptor antagonist M1-toxin and with pertussis toxin (PTX) treatment. Expression by nuclear cDNA injection of the regulator of G-protein signaling (RGS2) or a phospholipase Cβ1 C-terminal construct (PLCβ-ct) selectively reduced VI oxo-M modulation in PTX-treated and untreated cells. Expression of the Gβγ buffers transducin (Gαtr) and a G-protein-coupled-receptor kinase (GRK3) construct (MAS-GRK3) eliminated oxo-M modulation. Activation of the heterologously expressed neurokinin type 1 receptor, a Gαq/11-coupled receptor, resulted in VI calcium current modulation. This modulation was eliminated with coexpression of Gαtr or MAS-GRK3. Cells expressing Gβ1γ2 were tonically inhibited via the VD pathway. Application of oxo-M to these cells produced VI modulation and reduced the amount of current inhibited via the VD pathway. Together, these results confirm the requirement for Gβγ in VD modulation and implicate Gαq-GTP and Gβγ as components in the potentially novel VI pathway.