Electrophysiological characterization of the M-current in rat hypoglossal motoneurons

The M-current (I_M) is a voltage-dependent, persistent K⁺ current so termed because it is strongly inhibited by the cholinergic agonist muscarine. The I_M main function is to limit neuronal excitability by contrasting action potential firing. Although motoneurons are sensitive to acetylcholine, the role of I_M in modulating their excitability is still controversial. The aim of the present report was to examine the presence of I_M in 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 I_M deactivation voltage protocol or depolarizing current steps. Voltage commands from depolarized potential induced inward relaxations with the common characteristics of I_M, comprising inhibition by either muscarine (10μM) or the selective I_M inhibitor linopirdine (30μM). I_M was 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 I_M strongly regulated HM action potential firing, since both muscarine and linopirdine increased spike frequency whereas the M-channel opener retigabine (20μM) reduced it. Conversely, I_M seemed uninvolved in the generation of the medium afterhyperpolarizing potential. Our results suggest that HMs possess I_M, whose pharmacological modulation is an important tool to up- or down-regulate excitability, to be explored in experimental models of neurodegeneration.