Mechanisms of low-glucose sensitivity in carotid body glomus cells

OBJECTIVE-Glucose sensing is essential for the adaptive counterregulatory responses to hypoglycemia. We investigated the mechanisms underlying carotid body (CB) glomus cells activation by low glucose. RESEARCH DESIGN/METHODS AND RESULTS-Removal of extracellular glucose elicited a cell secretory response, abolished by blockade of plasma membrane Ca2+ channels, and a reversible increase in cytosolic Ca2+ concentration. These data indicated that glucopenia induces transmembrane Ca2+ influx and transmitter secretion. In patch-clamped glomus cells, exposure to low glucose resulted in inhibition of macroscopic outward K+ currents and in the generation of a depolarizing receptor potential (DRP). The DRP was abolished upon removal of extracellular Na+. The membrane-permeable 1-oleoyl-2-acetylsn-glycerol induced inward currents of similar characteristics as the current triggered by glucose deficiency. The functional and pharmacological analyses suggest that low glucose activates background cationic Na+-permeant channels, possibly of the transient receptor potential C subtype. Rotenone, a drug that occludes glomus cell sensitivity to hypoxia, did not abolish responsiveness to low glucose. The association of Glut2 and glucokinase, characteristic of some high glucose-sensing cells, did not seem to be needed for low glucose detection. CONCLUSIONS-Altogether, these data support the view that the CB is a multimodal chemoreceptor with a physiological role in glucose homeostasis.