Substance P modulation of hypoglossal motoneuron excitability during development: changing balance between conductances

Abstract

Although Substance P (SP) acts primarily through neurokinin 1 (NK1) receptors to increase the excitability of virtually all motoneurons (MNs) tested, the ontogeny of this transmitter system is not known for any MN pool. Hypoglossal (XII) MNs innervate tongue protruder muscles and participate in several behaviors that must be functional from birth including swallowing, suckling and breathing. We used immunohistochemistry, Western immunoblotting, and whole cell recording of XII MNs in brain stem slices from rats ranging in age from postnatal day zero (P0) to P23 to explore developmental changes in: NK1 receptor expression; currents evoked by SP(NK1) (an NK1-selective SP receptor agonist) and; the efficacy of transduction pathways transforming ligand binding into channel modulation. Despite developmental reductions in XII MN NK1 receptor expression, SP(NK1) current density remained constant at 6.1 +/- 1.0 (SE) pA/pF. SP(NK1) activated at least two conductances. Activation of a pH-insensitive Na(+) conductance dominated in neonates (P0-P5), but its contribution fell from approximately 80 to approximately 55% in juveniles (P14-P23). SP(NK1) also inhibited a pH-sensitive, two-pore domain K(+) (TASK)-like K(+) current. Its contribution increased developmentally. First, the density of this pH-sensitive K(+) current doubled between P0 and P23. Second, SP(NK1) did not affect this current in neonates, but reduced it by 20% at P7-P10 and 80% in juveniles. In addition, potentiation of repetitive firing was greatest in juveniles. These data establish that despite apparent reductions in NK1 receptor density, SP remains an important modulator of XII MN excitability throughout postnatal development due, in part, to increased expression of a pH-sensitive, TASK-like conductance.