Search

Hypoxia activates chemoreceptor cells of the carotid body (CB) promoting an increase in their normoxic release of neurotransmitters. Catecholamine (CA) release rate parallels the intensity of hypoxia. Coupling of hypoxia to CA release requires cell depolarization, produced by inhibition of [O.sub.2]-regulated [K.sup.+] channels, and [Ca.sup.2+] entering the cells via voltage-operated channels. In rat chemoreceptor cells hypoxia inhibits large-conductance, calcium-sensitive K channels (maxiK) and a two-pore domain weakly inward rectifying [K.sup.+] channel (TWIK)-like acid-sensitive [K.sup.+] channel (TASK)-like channel, but the significance of maxiK is controversial. A proposal envisions maxiK contributing to set the membrane potential ([E.sub.m]) and the hypoxic response, but the proposal is denied by authors finding that maxiK inhibition does not depolarize chemoreceptor cells or alters intracellular [Ca.sup.2+] concentration or CA release in normoxia or hypoxia. We found that maxiK channel blockers (tetraethylammonium and iberiotoxin) did not modify CA release in rat chemoreceptor cells, in either normoxia or hypoxia, and iberiotoxin did not alter the [Ca.sup.2+] transients elicited by hypoxia. On the contrary, both maxiK blockers increased the responses elicited by dinitrophenol, a stimulus we demonstrate does not affect maxiK channels in isolated patches of rat chemoreceptor cells. We conclude that in rat chemoreceptor cells maxiK channels do not contribute to the genesis of the [E.sub.m], and that their full inhibition by hypoxia, preclude further inhibition by maxiK channel blockers. We suggest that full inhibition of this channel is required to generate the spiking behavior of the cells in acute hypoxia. hypoxia; catecholamine; iberiotoxin; intracellular calcium

Carotid body (CB) chemoreceptor cells detect physiological levels of hypoxia and generate a hyperventilation, homeostatic in nature, aimed to minimize the deleterious effects of hypoxia. Intimate mechanisms involved in oxygen sensing in chemoreceptor cells remain largely unknown, but reactive oxygen species (ROS) had been proposed as mediators of this process. We have determined glutathione levels and calculated glutathione redox potential ([E.sub.GSH]; indicator of the general redox environment of cells) in rat diaphragms incubated in the presence of oxidizing agents of two types: nonpermeating and permeating through cell membranes; in the latter group, unspecific oxidants and inhibitors of ROS-disposing enzymes were used. Selected concentrations of oxidizing agents were tested for their ability to modify the normoxic and hypoxic activity of chemoreceptor cells measured in vitro as their rate of release of neurotransmitters. Results evidence variable relationships between [E.sub.GSH] and the activity of chemoreceptor cells. The independence of chemoreceptor cell activity from the [E.sub.GSH] would imply that the ability of the CB to play its homeostatic role is largely preserved in any pathological or toxicological contingency causing oxidative stress. Consistent with this suggestion, it was also found that CB-mediated hypoxic hyperventilation was not altered by treatment of intact animals with agents that markedly decreased the [E.sub.GSH] in all tissues assayed. oxygen sensing; carotid body; reactive oxygen species; hypoxia; reduced glutathione, oxidized glutathione; catecholamine; ventilation