Varied ionic currents underlie functional diversity of hypoglossal motoneurons innervating the superior longitudinalis and genioglossus tongue muscles

Abstract: Hypoglossal motoneurons (XIIMNs) control tongue movement, which must be precisely coordinated for communication, swallowing and respiration. We previously found that XIIMNs innervating intrinsic and extrinsic tongue muscles exhibit diverse firing properties. Here we investigate the mechanisms behind functional differences of XIIMNs that control the superior longitudinalis (SL) and genioglossus (GG) muscles, which retract and protrude the tongue, respectively. We hypothesized that varied ionic currents drive muscle-specific firing properties in XIIMNs. We obtained whole-cell patch-clamp recordings from retrogradely labelled SL and GG XIIMNs obtained from male and female neonatal rats. SL and GG XIIMNs exhibited distinct firing patterns, and SL XIIMNs had higher intrinsic excitability than GG XIIMNs. Next, voltage-clamp studies aimed to determine the ionic mechanisms responsible for functional differences between SL and GG XIIMNs. While whole-cell K⁺ conductance was similar in both populations, SL XIIMNs exhibited a large, sustained Ca²⁺-sensitive K⁺ current that was not observed in GG XIIMNs. Subsequent current-clamp studies evaluated the influence of Ca²⁺-sensitive K⁺ currents on firing behaviour. Bath application of the Ca²⁺ channel antagonist CdCl₂ produced opposite effects on firing behaviour in SL and GG XIIMNs. Ca²⁺ blockade impaired repetitive firing in SL XIIMNs and increased firing frequency in GG XIIMNs. These data indicate that distinct ionic currents contribute to the functional specialization of XIIMNs that control different tongue muscles. (Figure presented.). Key points: Using retrograde labelling and electrophysiology, we found that hypoglossal motoneurons innervating the superior longitudinalis (SL) and genioglossus (GG) muscles exhibit distinct biophysical properties. Until recently, hypoglossal motoneurons have been considered functionally homogeneous. Motoneurons innervating the SL had depolarized resting membrane potentials, lower firing thresholds and steeper frequency–current curves than GG motoneurons. SL motoneurons exhibited a prominent calcium-sensitive potassium current that was not observed in GG motoneurons. Calcium channel blockade differentially affected firing behaviour in SL and GG motoneurons. While SL motoneurons exhibited impaired repetitive discharge, GG motoneurons displayed increased firing frequency. Our findings suggest that hypoglossal motoneurons exhibit functional specialization, with distinct intrinsic membrane properties tailored to the specific motor demands of the tongue muscles they innervate.