Neuro-glial communication in NTS after hypoxia

Abstract

Humans ascending to high altitudes are submitted to sustained hypoxia (SH), which activates the peripheral chemoreflex with several autonomic and respiratory responses. In this study we analyzed initially the effect of short-term SH (24 hours, FIO210%) on the processing of cardiovascular and respiratory reflexes using an in situ preparation of rats. SH increased both the sympatho-inhibitory and bradycardiac components of baroreflex and the sympathetic and respiratory responses of peripheral chemoreflex. The electrophysiological properties and synaptic transmission in the nucleus tractus solitarius (NTS) neurons, the first synaptic station of afferents of baro- and chemoreflexes, were evaluated using brainstem slices and whole-cell patch clamp. The 2nd-order NTS neurons were identified by previous application of fluorescent tracer onto carotid body for chemoreceptor afferents or onto aortic depressor nerve for baroreceptor afferents. SH increased the intrinsic excitability of NTS neurons. Delayed excitation, caused by A-type potassium current (IKA), was observed in most of NTS neurons from control rats. The IKA amplitude was higher in identified 2nd-order NTS neurons from control than in SH rats. SH also blunted the astrocytic inhibition of IKA in NTS neurons and increased the synaptic transmission in response to afferent fibers stimulation. The frequency of spontaneous excitatory currents was also increased in neurons from SH rats, indicating that SH increased the neurotransmission by pre-synaptic mechanisms. We conclude that short-term SH changed the glia-neuron interaction, increasing the excitability and excitatory transmission of NTS neurons, which may contribute to the observed increase in the reflex sensitivity of baro- and chemoreflex in in situ preparation. Financial support: FAPESP and CNPq.