AU  - Kammermeier, Paul J.
AU  - Ruiz-Velasco, Victor
AU  - Ikeda, Stephen R.
TI  - A Voltage-Independent Calcium Current Inhibitory Pathway Activated by Muscarinic Agonists in Rat Sympathetic Neurons Requires Both Gαq/11 and Gβγ
PT  - JOURNAL ARTICLE
DP  - 2000 Aug 01 
TA  - The Journal of Neuroscience 
PG  - 5623-5629 
VI  - 20 
IP  - 15 
4099 - http://www.jneurosci.org/content/20/15/5623.abstract 
4100 - http://www.jneurosci.org/content/20/15/5623.full 
SO - J. Neurosci. 2000 Aug 01; 20(15):5623-5629 
AID  - 10.1523/JNEUROSCI.20-15-05623.2000 [doi] 
AB  - 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.