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.
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.
García-Fernández
María
M
Laboratorio de Investigaciones Biomédicas, Departamento de Fisiología Médica y Biofísica, Hospital Universitario Virgen del Rocío, Universidad de Sevilla, Sevilla, Spain.
Ortega-Sáenz
Patricia
P
Castellano
Antonio
A
López-Barneo
José
J
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002344:Carotid Body / Q000166:cytology* / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D003600:Cytosol / Q000378:metabolism; D017931:DNA Primers; D004594:Electrophysiology; D005947:Glucose / Q000494:pharmacology*; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics; D007003:Hypoglycemia / Q000503:physiopathology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D010234:Paraganglia, Nonchromaffin / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification; D051381:Rats; D017208:Rats, Wistar