CO2 decreases membrane conductance and depolarizes neurons in the nucleus tractus solitarii

Abstract

To identify central sites of potential CO2/H+-chemoreceptive neurons, and the mechanism responsible for neuronal chemosensitivity, intracellular recordings were made in rat tissue slices in two cardiopulmonary-related regions (i.e., nucleus tractus solitarii, NTS; nucleus ambiguus, AMBc) during exposure to high CO2. When the NTS was explored slices were bisected and the ventral half discarded. Utilizing such "dorsal" medullary slices removed any impinging synaptic input from putative chemoreceptors in the ventrolateral medulla. In the NTS, CO2-induced changes in firing rate were associated with membrane depolarizations ranging from 2-25 mV (n = 15). In some cases increased e.p.s.p. activity was observed during CO2 exposure. The CO2-induced depolarization occurred concomitantly with an increased input resistance ranging from 19-23 M omega (n = 5). The lower membrane conductance during hypercapnia suggests that CO2-induced depolarization is due to a decreased outward potassium conductance. Unlike neurons in the NTS, AMBc neurons were not spontaneously active and were rarely depolarized by hypercapnia. Eleven of 12 cells tested were either hyperpolarized by or insensitive to CO2. Only 1 neuron in the AMBc was depolarized and it also showed an increased input resistance during CO2 exposure. Our findings suggest that CO2/H+-related stimuli decrease potassium conductance which depolarizes the cell and increases firing rate. Although our in vitro studies cannot guarantee the specific function of these cells, we believe they may be involved with brain pH homeostasis and cardiopulmonary regulation.

Characterization of the chemosensitive response of individual solitary complex neurons from adult rats

“…In neonates, about 50% of caudal SC neurons are activated with a CI of about 150%, and about 10 -15% are inhibited with a CI of 57 Ϯ 6% (5). Studies done on SC neurons from adult rats have only looked at the percentage of neurons that were activated by HA (7,10,21,22). In a mix of caudal and more rostral slices, 35% of SC neurons from adult rats were found to be activated in response to HA (7), while in caudal slices only, 53% of SC neurons from adult rats were activated in response to HA (22).…”

“…PUTATIVE CENTRAL CHEMOSENSITIVE neurons have mostly been studied in neonatal rats in various localized regions within the brain stem, including the solitary complex [SC, including neurons from both the nucleus tractus solitarius (NTS) and the dorsal motor nucleus of the vagus (DMN)] (5,7,10,22), ventrolateral medulla (54), retrotrapezoid nucleus (RTN) (24,44), medullary raphé (40,53), pre-Bötzinger region (47), and the locus coeruleus (LC) (14,32,35). All of these regions increase ventilation when focally acidified (4,26).…”

Ventilatory effects of substance P-saporin lesions in the nucleus tractus solitarii of chronically hypoxic rats

“…We targeted the caudal NTS located under the area postrema as the location where the majority of CO 2 -sensitive neurons in the NTS complex have been identified in vitro (13,14). However, ϳ20% of chemoreceptors identified in medullary slices studied in vitro were located in the rostral NTS (13), and these would have been spared by our lesions.…”

“…The functional evidence for CO 2 sensitivity in the NTS is the same as it is for other sites. CO 2 -sensitive cells have been identified in vitro (14), and stimulating the CO 2 -sensitive cells with either microinjected acetazolamide (11) or microdialized CO 2 (43) increases V I in rats. The lack of effect of our lesion could indicate that the NK1R-positive cells are not involved in CO 2 sensing in the NTS: they comprise only a portion of the chemoreceptor cells in the NTS (see Critique of method above), or they are redundant to CO 2 sensitivity at other sites.…”

“…First, chronic hypoxia changes the ventilatory response to CO 2 (60), and the NTS contains CO 2 -sensitive cells (11,14,43). Also, the NTS receives the first synapse from O 2 -sensitive afferents from the carotid bodies (15,21,22,33,59), and this could lead to hypoxic or activity-dependent plasticity that has been demonstrated in the central nervous system with chronic hypoxia (16,49,62).…”