A voltage-independent calcium current inhibitory pathway activated by muscarinic agonists in rat sympathetic neurons requires both Gα(q/11) and Gβγ

Paul J. Kammermeier, Victor Ruiz-Velasco, Stephen R. Ikeda

Research output: Contribution to journalArticle

80 Scopus citations

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 (Gα(tr)) 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 Gα(q/11)-coupled receptor, resulted in VI calcium current modulation. This modulation was eliminated with coexpression of Gα(tr) or MAS-GRK3. Cells expressing Gβ12) 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 Gα(q)-GTP and Gβγ as components in the potentially novel VI pathway.

Original languageEnglish (US)
Pages (from-to)5623-5629
Number of pages7
JournalJournal of Neuroscience
Volume20
Issue number15
DOIs
StatePublished - Aug 1 2000

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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