Mechanisms of low-glucose sensitivity in carotid body glomus cells

Abstract

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 Ca(2+) channels, and a reversible increase in cytosolic Ca(2+) concentration. These data indicated that glucopenia induces transmembrane Ca(2+) 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-acetyl-sn-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.