title: Muscarinic modulation of TREK currents in mouse sympathetic superior cervical ganglion neurons.
abstract: Muscarinic receptors play a key role in the control of neurotransmission in the autonomic ganglia, which has mainly been ascribed to the regulation of potassium M-currents and voltage-dependent calcium currents. Muscarinic agonists provoke depolarization of the membrane potential and a reduction in spike frequency adaptation in postganglionic neurons, effects that may be explained by M-current inhibition. Here, we report the presence of a riluzole-activated current (IRIL ) that flows through the TREK-2 channels, and that is also inhibited by muscarinic agonists in neurons of the mouse superior cervical ganglion (mSCG). The muscarinic agonist oxotremorine-M (Oxo-M) inhibited the IRIL by 50%, an effect that was abolished by pretreatment with atropine or pirenzepine, but was unaffected in the presence of himbacine. Moreover, these antagonists had similar effects on single-channel TREK-2 currents. IRIL inhibition was unaffected by pretreatment with pertussis toxin. The protein kinase C blocker bisindolylmaleimide did not have an effect, and neither did the inositol triphosphate antagonist 2-aminoethoxydiphenylborane. Nevertheless, the IRIL was markedly attenuated by the phospholipase C (PLC) inhibitor ET-18-OCH3. Finally, the phosphatidylinositol-3-kinase/phosphatidylinositol-4-kinase inhibitor wortmannin strongly attenuated the IRIL , whereas blocking phosphatidylinositol 4,5-bisphosphate (PIP2 ) depletion consistently prevented IRIL inhibition by Oxo-M. These results demonstrate that TREK-2 currents in mSCG neurons are inhibited by muscarinic agonists that activate M1 muscarinic receptors, reducing PIP2 levels via a PLC-dependent pathway. The similarities between the signaling pathways regulating the IRIL and the M-current in the same neurons reflect an important role of this new pathway in the control of autonomic ganglia excitability.
authors.affiliation: Department of Functional Biology and Health Sciences, Faculty of Biology - CINBIO-IBIV, University of Vigo, Campus Lagoas-Marcosende, 36310, Vigo, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Rivas-Ramírez
authors.affiliation: Department of Functional Biology and Health Sciences, Faculty of Biology - CINBIO-IBIV, University of Vigo, Campus Lagoas-Marcosende, 36310, Vigo, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Cadaveira-Mosquera
authors.affiliation: Department of Functional Biology and Health Sciences, Faculty of Biology - CINBIO-IBIV, University of Vigo, Campus Lagoas-Marcosende, 36310, Vigo, Spain.
authors.forename: J A
authors.initials: JA
authors.lastname: Lamas
authors.affiliation: Department of Functional Biology and Health Sciences, Faculty of Biology - CINBIO-IBIV, University of Vigo, Campus Lagoas-Marcosende, 36310, Vigo, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Reboreda
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002586:Cesium / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D018678:Cholinergic Agents / Q000494:pharmacology; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D008297:Male; D051379:Mice; D009474:Neurons / Q000187:drug effects*; D010095:Oxotremorine / Q000031:analogs & derivatives / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D037342:Pertussis Toxin / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024683:Potassium Channels, Tandem Pore Domain / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000378:metabolism*; D019782:Riluzole / Q000494:pharmacology; D026941:Sodium Channel Blockers / Q000494:pharmacology; D017783:Superior Cervical Ganglion / Q000166:cytology*; D019789:Tetraethylammonium / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D002712:Chlorides; D018678:Cholinergic Agents; D018691:Excitatory Amino Acid Antagonists; D026902:Potassium Channel Blockers; D024683:Potassium Channels, Tandem Pore Domain; D011976:Receptors, Muscarinic; D026941:Sodium Channel Blockers; C103742:potassium channel protein TREK-1; D002586:Cesium; D013779:Tetrodotoxin; D010095:Oxotremorine; C042743:oxotremorine M; D019789:Tetraethylammonium; D019782:Riluzole; D037342:Pertussis Toxin; C028019:cesium chloride
keywords: PIP
  2; TREK-2; muscarinic receptor; potassium channel; two-pore domain potassium channel