Dependence of carotid chemosensory responses on metabolic substrates

Abstract

The dependence of the carotid chemosensory response to hypoxia on metabolic substrate and the hypothesis that lactic acidosis is essential for O 2 chemoreception were tested. Effects of 3 types of substrate (glucose, glutamate and a mixture of amino acids) on the response to hypoxia (perfusare flow interruption) were measured ( n = 33 carotid bodies). The response to nicotine ( n = 25) was used to determine whether these effects were exclusive to the hypoxic response. The cat carotid body was perfused and superfused in vitro with modified Tyrode solution ( pO 2 > 400 Torr, pCO 2 < 1 Torr, pH = 7.4) at 36°C containing a given substrate for at least 15 min prior to flow interruption or nicotine injection. Without substrate, responses to flow interruption ( n = 4) and nicotine ( n = 2) were irreversibly depressed. With glucose, responses to flow interruption ( n = 13) and nicotine ( n = 8) increased in a concentration-dependent fashion. Glutamate (42 mM) alone ( n = 11) or a mixture of amino acids (4.2 mM) plus 5.5 mM glucose ( n = 12) substituted for 11 mM glucose ( n = 10). Thus, glutamate (42 mM), or a mixture of amino acids (4.2 mM) or a high concentration of glucose (11 mM) can support chemosensory responses to flow interruption and nicotine. Since glutamate undergoes oxidative deamination to α-ketoglutarate without lactic acid production, O 2 chemoreception does not depend on lactic acidosis.