Mechanisms of Low-Glucose Sensitivity in Carotid Body Glomus Cells

Mechanisms of Low-Glucose Sensitivity in Carotid Body Glomus Cells María García-Fernández , Patricia Ortega-Sáenz , Antonio Castellano and José López-Barneo From the Laboratorio de Investigaciones Biomédicas, Departamento de Fisiología Médica y Biofísica, and Hospital Universitario Virgen del Rocío, Universidad de Sevilla, Sevilla, Spain Address correspondence and reprint requests to Dr. José López-Barneo, Laboratorio de Investigaciones Biomédicas, Edificio de Laboratorios, 2 a planta, Hospital Universitario Virgen del Rocío, Avda. Manuel Siurot s/n, E-41013 Sevilla, Spain. E-mail: jose.l.barneo.sspa{at}juntadeandalucia.es 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. CB, carotid body TRP, transient receptor potential TRPC, TRP C subtype Footnotes Published ahead of print at http://diabetes.diabetesjournals.org on 7 September 2007. DOI: 10.2337/db07-0122. M.G.-F. is currently affiliated with the Howard Hughes Medical Institute and The Rockefeller University, Laboratory of Apoptosis and Cancer Biology, New York, New York.