Hypercapnia and hypoxia: Chemoreceptor-mediated control of locus coeruleus neurons and splanchnic, sympathetic nerves

Abstract

Utilizing single cell recording techniques to study brain norepinephrine (NE) neurons in the locus coeruleus (LC) and, in the same rats, registration of splanchnic nerve activity (SNA) the effects on these systems of hypercapnia and hypoxia, respectively, were studied. Hypercapnia (pCO 2 36–103 mm Hg) caused a rapid increase in the firing rate of LC neurons as well as in SNA. This effect was directly correlated with the added amount of CO 2 in the inspired gas mixture. This finding indicates a similar chemoreceptor-mediated regulation of LC neurons and SNA. Since deafferentation of peripheral chemoreceptors did not alter the response of these systems to hypercapnia, the chemoreceptors involved must be centrally located. In hypoxia (pO 2 105-31 mm Hg) the overall effect on LC neurons was activation, whereas SNA was reduced. These effects were, however, not dose-dependent. Peripheral receptor deafferentation abolished the activation by hypoxia, suggesting that the LC neurons are influenced also by peripheral chemoreceptors. The results indicate that the previously observed increase in brain NE turnover in hypercapnia is largely secondary to increased neuronal activity and not due to, e.g., changes in metabolic enzymes. In addition, the data implicate chemoreceptors, centrally but also peripherally located, in the regulation of brain NE neurons in the LC. The activation of these neurons in hypercapnia, generally associated with increased apprehension in man, is consistent with the notion that the LC may serve as an alarm system in the brain.