Translating blood-borne stimuli: chemotransduction in the carotid body

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Prem KUMAR B.Sc.()
Journal Title:
Volume 59, Issue 02, 2007
Key Word:
carotid body;chemoreceptor;hypoxia;chemotransduction;AMP-activated protein kinase;glucose

Abstract: The carotid body can transduce hypoxia and other blood-borne stimuli, perhaps including hypoglycaemia, into afferent neural discharge that is graded for intensity and which forms the afferent limb of a cardiorespiratory and neuroendocrine reflex loop.Hypoxia inhibits a variety of K+ channels in the type Ⅰ cells of the carotid body, in a seemingly species-dependent manner, and the resultant membrane depolarisation is sufficient to activate voltage-gated Ca2+ entry leading to neurosecretion and afferent discharge.The ion channels that respond to hypoxia appear to do so indirectly and recent work has therefore focussed upon identification of other proteins in the type Ⅰ cells of the carotid body that may play key roles in the oxygen sensing process. Whilst a role for mitochondrial and/or NADPH-derived reactive oxygen species (ROS) has been proposed, the evidence for their signalling hypoxia in the carotid body is presently less than compelling and two alternate hypotheses are currently being tested further. The first implicates haemoxygenase 2 (HO-2), which may control specific K+ channel activation through O2-dependent production of the signalling molecule, carbon monoxide. The second hypothesis suggests a role for the cellular energy sensor, AMP-activated protein kinase (AMPK), which can inhibit type Ⅰ cell K+ channels and increase afferent discharge when activated by hypoxia-induced elevations in the AMP:ATP ratio. The apparent richness of O2-sensitive K+ channels and sensor mechanisms within this organ may indicate a redundancy system for this vital cellular process or it may be that each protein contributes differently to the overall response, for example, with different O2 affinities.The mechanism by which low glucose is sensed is not yet known, but recent evidence suggests that it is not via closure of K+ channels,unlike the hypoxia transduction process.

  • [1]Wilson RJ,Chersa T,Whelan PJ.Tissue PO2 and the effects of hypoxia on the generation of locomotor-like activity in the in vitro spinal cord of the neonatal mouse.Neuroscience 2003; 117(1):183-196.
  • [2]Semenza GL.O2-regulated gene expression:transcriptional control of cardiorespiratory physiology by HIF-1.J Appl Physiol 2004; 96(3):1173-1177; discussion:1170-1172.
  • [3]Gonzalez C,Almaraz L,Obeso A,Rigual R.Carotid body chemoreceptors:from natural stimuli to sensory discharges.Physiol Rev 1994; 74(4):829-898.
  • [4]Perez-Garcia MT,Colinas O,Miguel-Velado E,MorenoDominguez A,Lopez-Lopez JR.Characterization of the Kv channels of mouse carotid body chemoreceptor cells and their role in oxygen sensing.J Physiol 2004; 557(Pt 2):457-471.
  • [5]Peers C.Hypoxic suppression of K+ currents in type Ⅰ carotid body cells:selective effect on the Ca2+-activated K+ current.Neurosci Lett 1990; 119(2):253-256.
  • [6]Overholt JL,Ficker E,Yang T,Shams H,Bright GR,Prabhakar NR.HERG-like potassium current regulates the resting membrane potential in glomus cells of the rabbit carotid body.J Neurophysiol 2000; 83(3):1150-1157.
  • [7]Buckler KJ,Williams BA,Honore E.J Physiol 2000; 83(3):135-142.
  • [8]Wyatt CN,Buckler KJ.The effect of mitochondrial inhibitors on membrane currents in isolated neonatal rat carotid body type Ⅰ cells.J Physiol 2004; 556(Pt 1):175-191.
  • [9]Barbe C,Al-Hashem F,Conway AF,Dubuis E,Vandier C,Kumar P.A possible dual site of action for carbon monoxide-mediated chemoexcitation in the rat carotid body.J Physiol 2002; 543(Pt 3):933-945.
  • [10]Williams SE,Wootton P,Mason HS,Bould J,Iles DE,Riccardi D,Peers C,Kemp PJ.Hemoxygenase-2 is an oxygen sensor for a calcium-sensitive potassium channel.Science 2004; 306(5704):2093-2097.
  • [11]Ortega-Saenz P,Pascual A,Gomez-Diaz R,Lopez-Barneo J.Acute oxygen sensing in heme oxygenase-2 null mice.J Gen Physio12006; 128(4):405-411.
  • [12]Biscoe TJ,Duchen MR.Responses of type Ⅰ cells dissociated from the rabbit carotid body to hypoxia.J Physiol 1990; 428:39-59.
  • [13]Wilson DF,Mokashi A,Chugh D,Vinogradov S,Osanai S,Lahiri S.The primary oxygen sensor of the cat carotid body is cytochrome a3 of the mitochondrial respiratory chain.FEBS Lett 1994;351(3):370-374.
  • [14]Ortega-Saenz P,Pardal R,Garcia-Fernandez M,Lopez-Barneo J.Rotenone selectively occludes sensitivity to hypoxia in rat carotid body glomus cells.J Physiol 2003; 548(Pt 3):789-800.
  • [15]Piruat JI,Pintado CO,Ortega-Saenz P,Roche M,Lopez-Barneo J.The mitochondrial SDHD gene is required for early embryogenesis,and its partial deficiency results in persistent carotid body glomus cell activation with full responsiveness to hypoxia.Mol Cell Biol 2004; 24(24):10933-10940.
  • [16]Gonzalez C,Sanz-Alfayate G,Agapito MT,Gomez-Nino A,Rocher A,Obeso A.Significance of ROS in oxygen sensing in cell systems with sensitivity to physiological hypoxia.Respir Physiol Neurobiol 2002; 132(1):17-41.
  • [17]Acker H.Mechanisms and meaning of cellular oxygen sensing in the organism.Respir Physiol 1994; 95(1):1-10.
  • [18]Roy A,Rozanov C,Mokashi A,Daudu P,Al-mehdi AB,Shams H,Lahiri S.Mice lacking in gp91 phox subunit of NAD(P)H oxidase showed glomus cell[Ca2+]i and respiratory responses to hypoxia.Brain Res 2000; 872(1-2):188-193.
  • [19]He L,Chen J,Dinger B,Sanders K,Sundar K,Hoidal J,Fidone S.Characteristics of carotid body chemosensitivity in NADPH oxidase-deficient mice.Am J Physiol Cell Physiol 2002; 282(1):C27-C33.
  • [20]He L,Dinger B,Sanders K,Hoidal J,Obeso A,Stensaas L,Fidone S,Gonzalez C.Effect of p47phox gene deletion on ROS production and oxygen sensing in mouse carotid body chemoreceptor cells.Am J Physiol Lung Cell Mol Physiol 2005; 289(6):L916-L924.
  • [21]Williams BA,Buckler KJ.Biophysical properties and metabolic regulation of a TASK-like potassium channel in rat carotid body type 1 cells.Am J Physiol Lung Cell Mol Physiol 2004; 286(1):L221-L230.
  • [22]Hardie DG,Hawley SA,Scott JW.AMP-activated protein kinase-development of the energy sensor concept.J Physiol 2006;574(Pt 1):7-15.
  • [23]Kumar P,Peers C.AMP-activated protein kinase:function and dysfunction in health and disease.J Physiol 2006; 574(Pt 1):3-6.
  • [24]Evans AM,Mustard KJ,Wyatt CN,Peers C,Dipp M,Kumar P,Kinnear NP,Hardie DG.Does AMP-activated protein kinase couple inhibition of mitochondrial oxidative phosphorylation by hypoxia to calcium signaling in O2-sensing cells? J Biol Chem 2005; 280(50):41504-41511.
  • [25]Alvarez-Buylla R,de Alvarez-Buylla ER.Carotid sinus receptors participate in glucose homeostasis.Respir Physiol 1988; 72(3):347-359.
  • [26]Koyama Y,Coker RH,Stone EE,Lacy DB,Jabbour K,Williams PE,Wasserman DH.Evidence that carotid bodies play an important role in glucoregulation in vivo.Diabetes 2000; 49(9):1434-1442.
  • [27]Bin-Jaliah I,Maskell PD,Kumar P.Indirect sensing of insulininduced hypoglycaemia by the carotid body in the rat.J Physiol 2004; 556(Pt 1):255-266.
  • [28]Bin-Jaliah I,Maskell PD,Kumar P.Carbon dioxide sensitivity during hypoglycaemia-induced,elevated metabolism in the anaesthetized rat.J Physiol 2005; 563(Pt 3):883-893.
  • [29]Pardal R,Lopez-Barneo J.Low glucose-sensing cells in the carotid body.Nat Neurosci 2002; 5(3):197-198.
  • [30]Lopez-Barneo J.Oxygen and glucose sensing by carotid body glomus cells.Curr Opin Neurobiol 2003; 13(4):493-499.
  • [31]Nurse CA.Neurotransmission and neuromodulation in the chemosensory carotid body.Auton Neurosci 2005; 120(1-2):1-9.
  • [32]Almaraz L,Obeso A,Gonzalez C.Metabolic dissociation of carotid body chemoreceptors responses to different types of stimulation:Preliminary findings.In:The Peripheral Arterial Chemoreceptors.Pallot DJ.ed.1984,London,Croom Helm:141-151.
  • [33]Kumar P.How sweet it is:sensing low glucose in the carotid body.J Physiol 2007; 578(Pt 3):627.
  • [34]Zhang M,Buttigieg J,Nurse C.Neurotransmitter mechanisms mediating low-glucose signaling in co-cultures and fresh tissue slices of rat carotid body.J Physiol 2007 578(Pt 3):735-750.
  • [35]Lahiri S,DeLaney RG.Stimulus interaction in the responses of carotid body chemoreceptor single afferent fibers.Respir Physiol 1975; 24(3):249-266.
  • [36]Pepper DR,Landauer RC,Kumar P.Postnatal development of CO2-O2 interaction in the rat carotid body in vitro.J Physiol 1995;485 (Pt 2):531-541.
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