Autoactivity of A5 neurons: Role of subthreshold oscillations and persistent Na+ current

Abstract

A5 noradrenergic neurons play a key role in autonomic regulation, nociception, and respiration. The purpose of the present experiments was to characterize some of the intrinsic properties of A5 cells in vitro. Whole cell recordings were obtained from 85 spinally projecting neurons of the ventrolateral pens of neonate rats. Immunohistochemistry showed that 60% of the ventrolateral pontine cells were noradrenergic. Eighty percent of A5 neurons were spontaneously active (0.1-5.5 spikes/s). Their discharge rate was unchanged by a mixture of synaptic blockers that eliminated postsynaptic potentials (PSPs). The nonnoradrenergic cells could not be distinguished from A5 cells on the basis of discharge rate, action potential duration, inward rectification, input resistance, or accommodation. A5 cells displayed subthreshold irregular oscillations of the membrane potential (main frequency component 0.5-2 Hz). These oscillations were unchanged in the presence of low external Ca2+-high Mg2+ and were very reduced by hyperpolarizing the cells below -65 mV. The oscillations were partially attenuated by 1 μM tetrodotoxin (TTX) and were eliminated by reducing external Na+ (27 mM). Stepping the membrane potential from -65 to -50 mV for 200 ms revealed the presence of a transient and a persistent inward current that were both blocked by 0.1 μM TTX or by extracellular Na+ reduction. In conclusion, most A5 neurons are spontaneously active in vitro. They display irregular subthreshold membrane potential oscillations generated by voltage-activated conductances that include a persistent TTX-sensitive Na+ current. Most of the activity of A5 cells appears due to intrinsic properties rather than to synaptic inputs.