TY - JOUR T1 - A Voltage-Independent Calcium Current Inhibitory Pathway Activated by Muscarinic Agonists in Rat Sympathetic Neurons Requires Both Gα<sub>q/11</sub> and Gβγ JF - The Journal of Neuroscience JO - J. Neurosci. SP - 5623 LP - 5629 DO - 10.1523/JNEUROSCI.20-15-05623.2000 VL - 20 IS - 15 AU - Paul J. Kammermeier AU - Victor Ruiz-Velasco AU - Stephen R. Ikeda Y1 - 2000/08/01 UR - http://www.jneurosci.org/content/20/15/5623.abstract N2 - 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. ER -