title: Substance P Depolarizes Lamprey Spinal Cord Neurons by Inhibiting Background Potassium Channels.
abstract: Substance P is endogenously released in the adult lamprey spinal cord and accelerates the burst frequency of fictive locomotion. This is achieved by multiple effects on interneurons and motoneurons, including an attenuation of calcium currents, potentiation of NMDA currents and reduction of the reciprocal inhibition. While substance P also depolarizes spinal cord neurons, the underlying mechanism has not been resolved. Here we show that effects of substance P on background K+ channels are the main source for this depolarization. Hyperpolarizing steps induced inward currents during whole-cell voltage clamp that were reduced by substance P. These background K+ channels are pH sensitive and are selectively blocked by anandamide and AVE1231. These blockers counteracted the effect of substance P on these channels and the resting membrane potential depolarization in spinal cord neurons. Thus, we have shown now that substance P inhibits background K+ channels that in turn induce depolarization, which is likely to contribute to the frequency increase observed with substance P during fictive locomotion.
authors.affiliation: Nobel Institute for Neurophysiology, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Carolina
authors.initials: C
authors.lastname: Thörn Pérez
authors.affiliation: Nobel Institute for Neurophysiology, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Russell H
authors.initials: RH
authors.lastname: Hill
authors.affiliation: Nobel Institute for Neurophysiology, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Sten
authors.initials: S
authors.lastname: Grillner
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001095:Arachidonic Acids / Q000737:chemistry*; D015220:Calcium Channels / Q000378:metabolism; D004594:Electrophysiology; D063388:Endocannabinoids / Q000737:chemistry*; D007395:Interneurons / Q000502:physiology; D007798:Lampreys / Q000502:physiology*; D008124:Locomotion / Q000502:physiology; D008564:Membrane Potentials; D009046:Motor Neurons / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors; D009474:Neurons / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D053284:Polyunsaturated Alkamides / Q000737:chemistry*; D015221:Potassium Channels / Q000378:metabolism*; D024683:Potassium Channels, Tandem Pore Domain / Q000037:antagonists & inhibitors; D015398:Signal Transduction; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D013373:Substance P / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D001095:Arachidonic Acids; D015220:Calcium Channels; D063388:Endocannabinoids; D009419:Nerve Tissue Proteins; D053284:Polyunsaturated Alkamides; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; C420132:potassium channel subfamily K member 3; D013373:Substance P; C078814:anandamide