Muscarinic modulation of TREK currents in mouse sympathetic superior cervical ganglion neurons |
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| Authors: | P. Rivas‐Ramírez A. Cadaveira‐Mosquera J. A. Lamas A. Reboreda |
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| Affiliation: | Department of Functional Biology and Health Sciences, Faculty of Biology – CINBIO‐IBIV, University of Vigo, Vigo, Spain |
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| 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. |
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| Keywords: | muscarinic receptor
PIP
2
potassium channel TREK‐2 two‐pore domain potassium channel |
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