Participation of Na+ channels in the response of carotid body chemoreceptor cells to hypoxia

Abstract

The role played by Na+ channels of carotid body (CB) chemoreceptor cells was investigated by studying the effects of tetrodotoxin (TTX) on the release of 3H-labeled catecholamines ([3H]CA) by adult rabbit CBs previously incubated with the precursor [3H]tyrosine. TTX inhibited partially the release of [3H]CA elicited by mild hypoxia (10 or 7% O2) or by depolarizing incubation medium containing 20 or 30 mM KCl, but the response to more intense hypoxia (5 or 2% O2) or to higher KCl concentration (40 or 50 mM) was not significantly affected. The release of [3H]CA elicited by acidic stimuli, either 20% CO2 (pH 6.6) or the protonophore dinitrophenol (100 microM), although comparable in magnitude to that elicited by mild hypoxia, was not modified by TTX. These results provide evidence for the first time that Na+ channels of chemoreceptor cells participate in the transduction of hypoxic stimuli into the neurotransmitter release response of these cells and suggest that Na+ current operates as an amplifying device that enhances the initial cell depolarization mediated by the closure of the O2-sensitive K+ channels. Sympathetic denervation of CBs was followed by a marked reduction in the release of [3H]CA elicited by veratridine or by 20 mM KCl, suggesting that the number of Na+ channels in chemoreceptor cells decreases after denervation.

Oxygen Sensing in the Carotid Body

“…Obeso et al [24,25] showed that nitrendipine, a blocker of voltage-dependent Ca2+ channels, at a concentration of 0.5 pM, reduced by nearly 90% the release of DA elic ited by high external K+ and by nearly 85% that elicited by a moderate hypoxic stimulus, and Rocher et al [26] showed that veratridine, an activator of voltage-dependent Na+ channels elicited a release of DA which was dependent on the presence of Na+ and Ca2+ in the incubating solution and was completely blocked by tetrodotoxin (TTX; a blocker of Na+ channels). More recently it has also been shown that TTX partially blocks the release of DA elicited by hypoxia [27], Summarizing these findings, at the beginning of 1988 we had learnt that chemoreceptor cells are excita ble, that they possess a membrane potential dependent on K+, that they possess Na+, and Ca2+ channels operated by voltage, that low PO2 must depolarize chemoreceptor cells as a prerequisite to activate voltage-dependent Na+ and Ca2+ channels and that influx of Ca2+ required by hypoxia to elicit the release of DA occurs via voltage-dependent Ca2+.…”

Tetrodotoxin as a Tool to Elucidate Sensory Transduction Mechanisms: The Case for the Arterial Chemoreceptors of the Carotid Body

“…She showed further that veratridine induced release was nearly abolished by TTX, and most important, that low PO 2 -induced release also was partially inhibited by TTX. Her findings were communicated in early in 1987 to the Spanish Society of Biophysics, published as a short note in 1988 and as full length paper in 1994 [61,62,63]. Table 1 presents the status of our knowledge by the fall of 1987.…”

“…It should also be noted from Table 1 that even if Na + channels participate in the cascade of events that occurs between the low PO 2 detection and the neurosecretory response [63], this participation represents an amplifying signal because an important part of the response (≈60%) still remains when Na + channels are fully inhibited. Additionally, Table 1 shows that the participation of dihydropyridine sensitive channels in the entry of Ca 2+ to support hypoxia-induced release varies with the intensity of hypoxia, and finally, that even with mild hypoxia, some voltage-dependent pathways additional to L-type Ca 2+ channels participate in the stimulus- secretion coupling, because at any given hypoxic intensity the evoked release of DA is Ca 2+ dependent by more than 95%.…”

Developmental changes in chemoreceptor nerve activity and catecholamine secretion in rabbit carotid body: possible role of Na + and Ca 2+ currents

“…Na + currents play a major role in the magnitude of the secretory response of mature, rabbit carotid bodies to moderate hypoxia [24], and it was suggested that this current was not present in fetal cells [15]. Na + currents play a major role in the magnitude of the secretory response of mature, rabbit carotid bodies to moderate hypoxia [24], and it was suggested that this current was not present in fetal cells [15].…”

“…Previous studies have shown that the fast Na + current in rabbit glomus cells may play a major role in mediating depolarization [11,25], and can modulate the magnitude of catecholamine secretion in response to hypoxic stimuli [24]. We also began to address the cellular basis of developmental changes by examining age-dependent changes in the magnitude of Na + and Ca 2+ currents in isolated rabbit glomus cells.…”