Carotid body adaptation to hypoxia: cellular and molecular mechanisms in vitro.
Chronic hypoxia in vivo promotes long-term changes in the carotid body (CB) response to low PO2. By exposing cultured rat CB chemoreceptors (glomus cells) to 6% O2 for 1-3 weeks, we are investigating the cellular and molecular mechanisms of hypoxic adaptation. Recent studies have uncovered a series of plastic changes in glomus cells including hypertrophy, differential regulation of Na+, Ca2+, and K+ currents, and upregulation of the 'plasticity protein', GAP-43. We have also identified cyclic AMP as a possible intracellular mediator of at least some of these effects of chronic hypoxia. Associated with the changes in ionic currents, glomus cells become electrically more excitable. However, a complete understanding of the physiological response of chronically hypoxic glomus cells to chemostimuli will require more detailed knowledge of the specific alterations in the sensing and signaling pathways, including modifications in neurotransmitter (e.g. catecholamine) functions.
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Department of Biology, McMaster University, Hamilton, ON, Canada.
D000222:Adaptation, Physiological; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002344:Carotid Body / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D015687:Cell Hypoxia; D000242:Cyclic AMP / Q000502:physiology; D019922:GAP-43 Protein; D005786:Gene Expression Regulation / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D008564:Membrane Potentials; D018613:Microscopy, Confocal; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D009924:Organ Culture Techniques; D010100:Oxygen / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D012964:Sodium / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D019922:GAP-43 Protein; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D013779:Tetrodotoxin; D012964:Sodium; D000242:Cyclic AMP; D014446:Tyrosine 3-Monooxygenase; D011188:Potassium; D010100:Oxygen; D002118:Calcium