title: Electrophysiological characterization of the M-current in rat hypoglossal motoneurons.
abstract: The M-current (IM) is a voltage-dependent, persistent K+current so termed because it is strongly inhibited by the cholinergic agonist muscarine. The IMmain function is to limit neuronal excitability by contrasting action potential firing. Although motoneurons are sensitive to acetylcholine, the role of IMin modulating their excitability is still controversial. The aim of the present report was to examine the presence of IMin hypoglossal motoneurons (HMs) and its role in the modulation of firing properties using an in vitro model of rat brainstem slice. For this purpose, we employed the whole-cell patch-clamp technique to record HM responses upon stimulation with either a standard IMdeactivation voltage protocol or depolarizing current steps. Voltage commands from depolarized potential induced inward relaxations with the common characteristics of IM, comprising inhibition by either muscarine (10μM) or the selective IMinhibitor linopirdine (30μM). IMwas pharmacologically distinguished from the hyperpolarization-activated inward-rectifying current and, within the -20 to -50mV range, deactivated with >100-ms time constant. Current-clamp experiments demonstrated that IMstrongly regulated HM action potential firing, since both muscarine and linopirdine increased spike frequency whereas the M-channel opener retigabine (20μM) reduced it. Conversely, IMseemed uninvolved in the generation of the medium afterhyperpolarizing potential. Our results suggest that HMs possess IM, whose pharmacological modulation is an important tool to up- or down-regulate excitability, to be explored in experimental models of neurodegeneration.
authors.affiliation: Department of Neuroscience, International School for Advanced Studies (SISSA), via Bonomea, 265, 34136 Trieste, Italy. Electronic address: fghezzi@sissa.it.
authors.forename: Filippo
authors.initials: F
authors.lastname: Ghezzi
authors.affiliation: Department of Neuroscience, International School for Advanced Studies (SISSA), via Bonomea, 265, 34136 Trieste, Italy. Electronic address: scorsini@sissa.it.
authors.forename: Silvia
authors.initials: S
authors.lastname: Corsini
authors.affiliation: Department of Neuroscience, International School for Advanced Studies (SISSA), via Bonomea, 265, 34136 Trieste, Italy. Electronic address: nistri@sissa.it.
authors.forename: Andrea
authors.initials: A
authors.lastname: Nistri
mesh_terms: D000818:Animals; D007002:Hypoglossal Nerve / Q000187:drug effects / Q000502:physiology*; D007211:Indoles / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D009116:Muscarine / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D017208:Rats, Wistar; D046509:Tissue Culture Techniques
chemical_list: D007211:Indoles; D018377:Neurotransmitter Agents; D015221:Potassium Channels; D011725:Pyridines; D009116:Muscarine; C061017:linopirdine
keywords: KCNQ; brainstem; linopirdine; muscarine; retigabine; spike firing