The human carotid body: expression of oxygen sensing and signaling genes of relevance for anesthesia.
BACKGROUND
Hypoxia is a common cause of adverse events in the postoperative period, where respiratory depression due to residual effects of drugs used in anesthesia is an important underlying factor. General anesthetics and neuromuscular blocking agents reduce the human ventilatory response to hypoxia. Although the carotid body (CB) is the major oxygen sensor in humans, critical oxygen sensing and signaling pathways have been investigated only in animals so far. Thus, the aim of this study was to characterize the expression of key genes and localization of their products involved in the human oxygen sensing and signaling pathways with a focus on receptor systems and ion channels of relevance in anesthesia.


METHODS
Six CBs were removed unilaterally from patients undergoing radical neck dissection. The gene expression and cell-specific protein localization in the CBs were investigated with DNA microarrays, real-time polymerase chain reaction, and immunohistochemistry.


RESULTS
We found gene expression of the oxygen-sensing pathway, heme oxygenase 2, and the K channels TASK (TWIK-related acid sensitive K channel)-1 and BK (large-conductance potassium channel). In addition, we show the expression of critical receptor subunits such as γ-aminobutyric acid A (α2, β3, and γ2), nicotinic acetylcholine receptors (α3, α7, and β2), purinoceptors (A2A and P2X2), and the dopamine D2 receptor.


CONCLUSIONS
In unique samples of the human CB, we here demonstrate presence of critical proteins in the oxygen-sensing and signaling cascade. Our findings demonstrate similarities to, but also important differences from, established animal models. In addition, our work establishes an essential platform for studying the interaction between anesthetic drugs and human CB chemoreception.
Fagerlund
Malin Jonsson
MJ
Section for Anesthesiology and Intensive Care Medicine, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden. malin.jonsson.fagerlund@ki.se
Kåhlin
Jessica
J
Ebberyd
Anette
A
Schulte
Gunnar
G
Mkrtchian
Souren
S
Eriksson
Lars I
LI
D000328:Adult; D000368:Aged; D000758:Anesthesia; D018685:Anesthetics, Inhalation; D002344:Carotid Body / Q000502:physiology*; D005260:Female; D015870:Gene Expression / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008738:Methyl Ethers; D046228:Microarray Analysis; D008875:Middle Aged; D037981:Neck Dissection; D010101:Oxygen Consumption / Q000235:genetics* / Q000502:physiology*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000235:genetics / Q000502:physiology; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D011950:Receptors, Cholinergic / Q000235:genetics / Q000502:physiology; D011954:Receptors, Dopamine / Q000235:genetics / Q000502:physiology; D018079:Receptors, GABA / Q000235:genetics / Q000502:physiology; D011983:Receptors, Purinergic / Q000235:genetics / Q000502:physiology; D012121:Respiration, Artificial; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077149:Sevoflurane; D015398:Signal Transduction / Q000235:genetics* / Q000502:physiology*
D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D015221:Potassium Channels; D011950:Receptors, Cholinergic; D011954:Receptors, Dopamine; D018079:Receptors, GABA; D011983:Receptors, Purinergic; D000077149:Sevoflurane; D012313:RNA