Vasopressin generates a persistent voltage-dependent sodium current in a mammalian motoneuron

Abstract

During the period of life that precedes weaning, the facial nucleus of the newborn rat is rich in 3H-vasopressin binding sites, and exogenous arginine vasopressin (AVP) can excite facial motoneurons by interacting with V1 (vasopressor-type) receptors. We have investigated the mode of action of this peptide by carrying out single-electrode voltage-clamp recordings in coronal brainstem slices from the neonate. Facial motoneurons were identified by antidromic invasion following electrical stimulation of the genu of the facial nerve. When the membrane potential was held at or near its resting level, vasopressin generated an inward current whose magnitude was concentration related; the lowest peptide concentration still effective in eliciting this effect was 10 nM. The vasopressin-induced current, IAVP, was resistant to tetrodotoxin (TTX) and was insensitive to a reduction in extracellular calcium concentration. It was sustained, was inward at all potentials tested (-120 to -25 mV), and increased in magnitude during depolarization. IAVP was not generated by the blockade of a potassium current, because it did not reverse at hyperpolarized potentials, was not affected by a two-fold increase in the transmembrane potassium gradient, and was not modified by the potassium channel blockers tetraethylammonium bromide (TEA), 4-aminopyridin (4-AP), barium, cesium, quinine, glibenclamide, and apamin. Also, IAVP was not affected by changes in the transmembrane chloride gradient. In contrast, it could be reduced by partially substituting extracellular sodium with equimolar N-methyl-D-glucamine or Tris. Our results suggest that vasopressin increases the excitability of facial motoneurons by generating a persistent sodium-dependent membrane current that is voltage gated and TTX resistant.

Synaptic Control of Motoneuronal Excitability

“…These effects are blocked by an AVP receptor antagonist and mimicked by a V 1 but not a V 2 receptor agonist (956,1019,1269). Together with the receptor binding data presented above (956,1269), these results indicate that AVP acts via a V 1a receptor to depolarize and increase the excitability of neonatal motoneurons.…”

“…In neonatal rat brain stem slice preparations, AVP increases the firing rate of facial motoneurons and induces the development of an inward current in both facial and hypoglossal motoneurons (956,1019,1269). These effects are blocked by an AVP receptor antagonist and mimicked by a V 1 but not a V 2 receptor agonist (956,1019,1269).…”

“…Subsequently, excitatory effects of both AVP and oxytocin have been documented in other neonatal motoneurons (956,1019,1269). Although the receptor and ionic mechanisms for effects of AVP have been studied most extensively, oxytocin and AVP each invokes inward currents that are similar in magnitude and time course in the same neonatal hypoglossal motoneurons, suggesting that they may share a common mechanism (956).…”

Mechanism of action of oxytocin in rat vagal neurones: induction of a sustained sodium‐dependent current.

“…In antidromically identified facial motoneurones, vasopressin generated a concentration-dependent inward current which was persistent, voltage gated and TTX resistant (Raggenbass, Goumaz, Sermasi, Tribollet & Dreifuss, 1991). This current could be reduced or suppressed by partial substitution of extracellular sodium by N-methyl-D-glucamine or Tris.…”

Nicotinic receptors in circuit excitability and epilepsy

“…In striking contrast, axotomized motoneurons displayed little or no sensitivity to ACh. Axotomy did not affect the sensitivity of VII motoneurons to the glutamate receptor agonists AMPA or NMDA or to the neuropeptide vasopressin-which excites VII motoneurons by generating a sodium-dependent inward current (Raggenbass et al, 1991). Immunohistochemical studies revealed that the ␣4 nicotinic receptor subunit was present in intact motoneurons but was undetectable in axotomized motoneurons.…”