HCN channels modulate the medium afterhyperpolarization and adjust the firing gain of fast alpha motoneurons in mice.

Motoneuron subtypes exhibit distinct firing properties that are critical for the graded control of muscle force. A key determinant of these differences is the medium afterhyperpolarization (mAHP), which shapes discharge rate and firing gain. Although subtype-specific variation in mAHP properties has traditionally been attributed to differences in small-conductance calcium-activated potassium (SK) channel expression, emerging evidence suggests that additional conductances may contribute. Here, we investigated the role of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in regulating the mAHP and excitability of mouse spinal motoneurons during postnatal development. Using whole cell patch-clamp recordings obtained from lumbar motoneurons of 2- to 3-wk-old mice, we show that mAHP amplitude is negatively correlated with the magnitude of the h current (Ih) in fast motoneurons, where Ih is active at resting potential. Pharmacological blockade of HCN channels with ZD7288 increased mAHP amplitude in fast but not slow motoneurons, without affecting mAHP duration, indicating a subtype-specific contribution to mAHP amplitude. In line with the mAHP regulating firing gain, ZD7288 also reduced firing gain in fast but not in slow motoneurons. These findings support a contribution of HCN channel activity to the regulation of mAHP amplitude and firing gain in fast motoneurons, highlighting a potential interaction between Ih and SK channel-dependent mechanisms in shaping motoneuron excitability.NEW & NOTEWORTHY Fast and slow motoneurons differ in firing properties critical for force control, yet mechanisms underlying subtype-specific regulation of the medium afterhyperpolarization (mAHP) remain unclear. We show that hyperpolarization-activated cyclic nucleotide-gated (HCN) channel activity selectively constrains mAHP amplitude and firing gain in fast alpha motoneurons in mice, revealing Ih as an important contributor to subtype-specific excitability, providing a complementary mechanism to traditional small-conductance calcium-activated potassium (SK) channel regulation of the mAHP.