Estimation of persistent inward currents contribution to inspiratory motoneuron firing in humans

Persistent inward currents (PICs) are known to prolong firing of limb-muscle motoneurons. Although there is immunohistochemical evidence of PIC channels in respiratory motoneurons, it is unknown whether PICs contribute to their firing prolongation. Intramuscular electromyographic signals were recorded from human inspiratory muscles to identify motor unit (MU) activity. Diaphragm MUs were identified during quiet breathing (n = 7; one female) and MUs from the 1st, 3rd, and 5th parasternal intercostal muscles during quiet (no lung volume feedback) and voluntary (triangular-shaped lung volume feedback) breathing (n = 5 males). PIC contribution to firing prolongation was estimated via quantification of firing hysteresis (paired MU analysis; ∆F) and firing symmetry in relation to peak volume (duration ratio). Diaphragm was the only muscle in which MUs exhibited ∆F scores significantly greater than 1 Hz, suggesting a possible PIC contribution. The proportion of MUs firing into expiration (duration ratio < 1) was higher in diaphragm than in the 1st and 3rd intercostal muscles, but not different to the 5th. Duration ratios were higher in voluntary compared to quiet breaths in the 3rd and 5th intercostals, suggesting less firing prolongation. However, ∆F was not different between quiet and voluntary breaths in parasternal intercostal MUs. These findings suggest that PICs contribute to firing prolongation in diaphragm MUs during quiet breathing. However, PIC-like behaviours were not evident in parasternal intercostal MUs firing during either quiet or voluntary breathing. These data underscore potentially different levels of neuromodulation across inspiratory muscles and further advance our understanding of the neural mechanisms regulating respiratory muscle control. KEY POINTS: Spinal motoneurons transmit signals to muscles to regulate their contraction, and the intrinsic excitability of motoneurons is enhanced by persistent inward currents (PICs). PICs consist of a persistent flow of sodium and calcium ions into the motoneuron, which can help initiate, accelerate and prolong its firing. We investigated PIC contributions to motoneuron firing in human inspiratory muscles by analysis of diaphragm and parasternal intercostal motor unit activity during involuntary (quiet) and voluntary breathing. Diaphragm motor units showed a magnitude of firing prolongation consistent with a significant role of PICs in this muscle, whereas no such effect was observed in parasternal intercostal muscles. These findings suggest a differential contribution of PICs to motoneuron firing across different inspiratory muscles. Our study enhances understanding of respiratory muscle control and motivates future efforts to validate, further estimate or modulate possible PIC contributions to respiratory motoneuron firing in humans and animal models.