Note: Intro -- Preface -- Contents -- 1: Epigenetic Regulation of Carotid Body Oxygen Sensing: Clinical Implications -- 1.1 Introduction -- 1.2 Neonatal IH Augments Carotid Body and AMC Responses to Hypoxia -- 1.2.1 The Effects of Neonatal IH on the Carotid Body and AMC Persist into Adult Life and Their Consequences on Cardio-Respiratory Functions -- 1.3 Reactive Oxygen Species (ROS) - A Major Cellular Mechanism Mediating the Effects of Neonatal IH -- 1.4 Neonatal IH Initiates Epigenetic Programming of Redox State by DNA Methylation -- 1.4.1 Role of DNA Methyl Transferases in Regulating Anti-oxidant Gene Methylation -- 1.4.2 DNA Methyl Transferase Inhibitors Prevent the Long-­Lasting Effects of Neonatal IH -- 1.5 Summary and Perspective -- References -- 2: Experimental Observations on the Biological Significance of Hydrogen Sulfide in Carotid Body Chemoreception -- 2.1 Introduction -- 2.2 Material and Methods -- 2.2.1 Animals and Anaesthesia. Surgical Procedures -- 2.2.2 3H-Catecholamine (3H-CA) Release Experiments Using Intact CBs -- 2.2.3 cAMP Measurement -- 2.2.4 Statistics -- 2.3 Results -- 2.3.1 Sulfide and cAMP -- 2.3.2 Effects of TRPA1 Channel Inhibition of NaSH Elicited 3H-CA Release -- 2.4 Discussion -- References -- 3: The CamKKβ Inhibitor STO609 Causes Artefacts in Calcium Imaging and Selectively Inhibits BKCa in Mouse Carotid Body Type I Cells -- 3.1 Introduction -- 3.2 Methods -- 3.2.1 Type I Cell Isolation -- 3.2.2 N2A Cell Culture -- 3.2.3 Ca2+ Imaging -- 3.2.4 Electrophysiology -- 3.3 Results -- 3.3.1 Ca2+ Imaging -- 3.3.2 Electrophysiology -- 3.4 Discussion -- References -- 4: Tissue Dynamics of the Carotid Body Under Chronic Hypoxia: A Computational Study -- 4.1 Introduction -- 4.2 Materials and Methods -- 4.2.1 Animals and Experimental Procedure of Hypoxia Exposure. , 4.2.2 Tissue Samples and Immunohistochemistry -- 4.2.3 Morphometry -- 4.2.4 "Population Level" Modeling of the Carotid Body Changes Under Hypoxia -- 4.2.5 "Cell-Centered" Model of Carotid Body Changes Under Hypoxia -- 4.2.5.1 Simulation of the Initial (Normoxic) Pattern -- 4.2.5.2 Simulation of the Tissue Remodeling Under Hypoxic Conditions -- 4.3 Results -- 4.3.1 "Population Level" Model and Changes in Cell Composition -- 4.3.2 "Cell-Centered" Model and Changes in Tissue Architecture -- 4.4 Discussion -- References -- 5: Paracrine Signaling in Glial-Like Type II Cells of the Rat Carotid Body -- 5.1 Introduction -- 5.2 Materials and Methods -- 5.2.1 Cell Culture -- 5.2.2 Fura-2 Ratiometric Ca2+ Imaging -- 5.2.3 Electrophysiology -- 5.2.4 Solutions and Drugs -- 5.3 Results -- 5.3.1 Angiotensin II (ANG II) Stimulates a Rise in [Ca2+]i and Activates Panx-1 Currents in Type II Cells via AT1 Receptors -- 5.3.2 Endothelin 1 (ET-1) Stimulates a Rise in [Ca2+]i in Type II Cells -- 5.3.3 ACh Mobilizes Ca2+ and Activates Panx-1-Like Currents in Type II Cells -- 5.4 Discussion -- References -- 6: Selective mu and kappa Opioid Agonists Inhibit Voltage-Gated Ca2+ Entry in Isolated Neonatal Rat Carotid Body Type I Cells -- 6.1 Introduction -- 6.2 Methods -- 6.2.1 Type I Cell Isolation -- 6.2.2 Immunocytochemistry -- 6.2.3 Ca2+ Imaging -- 6.3 Results -- 6.3.1 Immunocytochemistry -- 6.3.2 Ca2+ Imaging -- 6.4 Discussion -- References -- 7: Measurement of ROS Levels and Membrane Potential Dynamics in the Intact Carotid Body Ex Vivo -- 7.1 Introduction -- 7.2 Methods -- 7.2.1 CB Preparation -- 7.2.2 Microscopy -- 7.2.3 ROS Sensitive HSP-FRET Construct -- 7.3 Results and Discussion -- References. , 8: Acutely Administered Leptin Increases [Ca2+]i and BKCa Currents But Does Not Alter Chemosensory Behavior in Rat Carotid Body Type I Cells -- 8.1 Introduction -- 8.2 Methods -- 8.2.1 Type I Cell Isolation -- 8.2.2 Ca2+ Imaging -- 8.2.3 Electrophysiology -- 8.2.4 Solutions -- 8.2.5 Statistics -- 8.3 Results -- 8.3.1 Ca2+ Imaging Experiments -- 8.3.2 Voltage Clamp Experiments -- 8.3.3 Current Clamp Experiments -- 8.4 Discussion -- References -- 9: Functional Properties of Mitochondria in the Type-1 Cell and Their Role in Oxygen Sensing -- 9.1 Introduction: Acute Oxygen Sensing -- 9.2 Stimulus Secretion Coupling in the Type-1 Cell -- 9.3 Role of Ion Channels -- 9.4 Role of Mitochondria in Oxygen Sensing -- 9.5 Mitochondrial Oxygen Sensitivity -- 9.6 New Evidence for High Oxygen Sensitivity in Type-1 Cell Mitochondria -- 9.7 Potential Mechanisms for Enhanced Mitochondrial Oxygen Sensitivity -- 9.7.1 Competitive Inhibitors: Nitric Oxide and Carbon Monoxide -- 9.7.2 Another "Master" Oxygen Sensing Pathway: Hydrogen Sulphide -- 9.7.3 An Alternative Cytochrome Oxidase -- 9.8 Signalling Between Mitochondria and Ion Channels -- 9.9 Conclusions -- References -- 10: Potentiation of Hypoxic Pulmonary Vasoconstriction by Hydrogen Sulfide Precursors 3-Mercaptopyruvate and D-Cysteine Is Blocked by the Cystathionine γ Lyase Inhibitor Propargylglycine -- 10.1 Introduction -- 10.2 Methods -- 10.2.1 Ethical Approval and Myography -- 10.2.2 HPV Experimental Protocol, Data Representation and Statistical Analysis -- 10.3 Results -- 10.4 Discussion -- References -- 11: Modulation of the LKB1-AMPK Signalling Pathway Underpins Hypoxic Pulmonary Vasoconstriction and Pulmonary Hypertension -- 11.1 Introduction -- 11.2 Mitochondria and Oxygen Sensing -- 11.3 The AMP-Activated Protein Kinase Mediates Hypoxic Pulmonary Vasoconstriction. , 11.4 The Lkb1-AMPK Signalling Cascade and HPV -- 11.5 The Lkb1-AMPK Signalling Cascade and the Development of Hypoxic Pulmonary Hypertension -- 11.6 Summary -- References -- 12: Organismal Responses to Hypoxemic Challenges -- 12.1 Introduction -- 12.2 Materials and Methods for Group 1 Cats -- 12.3 Materials and Methods for Groups 2, 3 Cats -- 12.4 Results for Group 1 Cats (Before and After Aortic Nerve Cutting) -- 12.5 Results for Group 2 (Intact), 3 (Aortic Nerves Transected) Cats -- 12.6 Discussion -- 12.7 Summary and Conclusions -- References -- 13: Effect of Lipopolysaccharide Exposure on Structure and Function of the Carotid Body in Newborn Rats -- 13.1 Introduction -- 13.2 Methods -- 13.2.1 Ventilation -- 13.2.2 Carotid Sinus Nerve Activity -- 13.2.3 Histology -- 13.3 Results -- 13.3.1 Ventilation -- 13.3.2 Carotid Sinus Nerve Activity -- 13.3.3 Histology -- 13.4 Discussion -- References -- 14: Hypoxic Ventilatory Reactivity in Experimental Diabetes -- 14.1 Introduction -- 14.2 Methods -- 14.2.1 Protocol of Functional Studies -- 14.2.2 Transmission Electron Microscopy -- 14.2.3 Laser Scanning Confocal Microscopy -- 14.3 Results and Discussion -- 14.4 Summary and Conclusions -- References -- 15: Adenosine Receptor Blockade by Caffeine Inhibits Carotid Sinus Nerve Chemosensory Activity in Chronic Intermittent Hypoxic Animals -- 15.1 Introduction -- 15.2 Methods -- 15.3 Results -- 15.4 Discussion -- References -- 16: Neurotrophic Properties, Chemosensory Responses and Neurogenic Niche of the Human Carotid Body -- 16.1 Introduction -- 16.2 Structure and GDNF Content of the Human CB -- 16.3 Cellular Responses to Hypoxia -- 16.4 Cellular Responses to Hypoglycemia -- 16.5 Neurogenic Niche in the Human Carotid Body -- 16.6 Conclusions -- References -- 17: Is the Carotid Body a Metabolic Monitor?. , 17.1 Introduction -- 17.2 Methods -- 17.2.1 Measurements of CSN Activity -- 17.2.2 Gene Expression Analysis -- 17.3 Results -- 17.3.1 CSN Chemoreceptor Activity -- 17.3.2 Gene Expression of TRP Channels -- 17.4 Discussion -- References -- 18: Lipopolysaccharide-Induced Ionized Hypocalcemia and Acute Kidney Injury in Carotid Chemo/Baro-Denervated Rats -- 18.1 Introduction -- 18.2 Materials and Methods -- 18.3 Results -- 18.3.1 Cardiorespiratory Changes After IP Administration of LPS -- 18.3.2 LPS-Induced AKI and Ionized Hypocalcemia -- 18.3.3 ECG Changes and Cardiac Markers in Septic Rats -- 18.4 Discussion -- References -- 19: Role of the Carotid Body Chemoreflex in the Pathophysiology of Heart Failure: A Perspective from Animal Studies -- 19.1 Introduction -- 19.2 Tonic Activation of the Carotid Body in CHF -- 19.2.1 Local Tissue and Humoral Factors -- 19.2.2 Hemodynamic Factors -- 19.2.3 Neural Factors -- 19.2.4 Ventilatory Factors -- 19.2.5 Temporal Sequence of Events -- 19.3 Functional Consequences of CB Activation in CHF -- 19.3.1 Autonomic Imbalance -- 19.3.2 Breathing Instability -- 19.3.3 Respiratory-Sympathetic Coupling -- 19.3.4 Cardiac Function -- 19.3.5 Renal function -- 19.4 Translational Impact of CB Hyperactivity in CHF -- 19.5 Conclusions -- References -- 20: A Short-Term Fasting in Neonates Induces Breathing Instability and Epigenetic Modification in the Carotid Body -- 20.1 Introduction -- 20.2 Methods -- 20.2.1 Measurements of Ventilation and Carotid Sinus Nerve (CSN) Activity -- 20.2.2 Assessment of Epigenetic Changes -- 20.3 Results -- 20.3.1 Breathing -- 20.3.2 CSN Chemoreceptor Activity -- 20.3.3 Epigenetic Modifications -- 20.4 Discussion -- References -- 21: Carotid Body Chemoreflex Mediates Intermittent Hypoxia-­Induced Oxidative Stress in the Adrenal Medulla -- 21.1 Introduction. , 21.2 Methods.

Note: Intro -- Arterial Chemoreception -- Preface -- A Tribute to Professor Sukhamay Lahiri: Past President of International Society for Arterial Chemoreceptors (ISAC) -- Contents -- Contributors -- Chapter 1: The Role of Hypoxia-Inducible Factors in Oxygen Sensing by the Carotid Body -- References -- Chapter 2: Neuronal Mechanisms of Oxygen Chemoreception: An Invertebrate Perspective -- 2.1 Introduction: Oxygen Sensing -- 2.2 Oxygen Sensing in Invertebrates -- 2.3 Lymnaea as a Model System -- 2.3.1 Aerial Respiratory Behaviour -- 2.3.2 The Respiratory Central Pattern Generator -- 2.3.3 Peripheral Oxygen Chemoreceptors Drive Aerial Respiration in Lymnaea -- 2.4 Future Perspectives -- References -- Chapter 3: Peripheral Chemoreceptors in Air- Versus Water- Breathers -- 3.1 Introduction -- 3.2 Phylogeny of the Aortic Arches -- 3.3 O 2 and CO 2 Receptors in the Gills of Water Breathers -- 3.3.1 Teleost Fish -- 3.3.2 Larval Amphibians -- 3.4 Peripheral O 2 and CO 2 /H + Chemoreceptors in Air Breathers -- 3.4.1 Mammalian Carotid and Aortic Bodies -- 3.4.2 Mammalian Glomus Cells as Polymodal Chemoreceptors -- 3.4.3 Perinatal Adrenal Chromaf n Cells as Polymodal Chemoreceptors -- References -- Chapter 4: Sex-Speci c Effects of Daily Gavage with a Mixed Progesterone and Glucocorticoid Receptor Antagonist on Hypoxic Ventilatory Response in Newborn Rats -- 4.1 Introduction -- 4.2 Methods -- 4.3 Results -- 4.4 Discussion -- References -- Chapter 5: Age-Dependent Changes in Breathing Stability in Rats -- 5.1 Introduction -- 5.2 Materials and Methods -- 5.3 Results -- 5.4 Discussion -- References -- Chapter 6: Dose Dependent Effect of Progesterone on Hypoxic Ventilatory Response in Newborn Rats -- 6.1 Introduction -- 6.2 Materials and Methods -- 6.3 Results -- 6.3.1 Progesterone Does Not Affect Baseline Ventilation and Metabolism. , 6.3.2 Dose- and Age-Dependent Effects of Progesterone on HVR and Metabolism -- 6.4 Discussion -- 6.5 Conclusions -- References -- Chapter 7: Postnatal Hyperoxia Impairs Acute Oxygen Sensing of Rat Glomus Cells by Reduced Membrane Depolarization -- 7.1 Introduction -- 7.2 Methods -- 7.2.1 Animal Model -- 7.2.2 Carotid Body Cell Isolation -- 7.2.3 Electrophysiological Studies -- 7.2.4 Quantitative Real Time PCR (qPCR) -- 7.3 Results -- 7.3.1 Effect of Hyperoxia-Exposure on Membrane Depolarization -- 7.3.2 Gene Expression Modulation by Postnatal Hyperoxia Exposure -- 7.4 Discussion -- References -- Chapter 8: Erythropoietin and the Sex-Dimorphic Chemore ex Pathway -- 8.1 Cerebral Erythropoietin Regulates Hypoxic Ventilation -- 8.2 Carotid Body Mediates the Hypoxic Ventilatory Response -- 8.3 Carotid Body Is a Sex Dimorphic Organ -- 8.4 Plasma EPO Interacts with Carotid Body Glomus Cells -- 8.5 EPO Modulates the Chemore ex in a Sex-Dependent Manner -- 8.6 Clinical Implications and Future Research -- References -- Chapter 9: Time-Course of Ventilation , Arterial and Pulmonary CO 2 Tension During CO 2 Increase in Humans -- 9.1 Introduction -- 9.2 Methods -- 9.2.1 Study subjects -- 9.2.2 Protocol -- 9.2.3 Fitting to Exponential Curve -- 9.2.4 Analysis -- 9.2.5 Statistics -- 9.3 Results -- 9.3.1 Changes in Pulmonary Hemodynamics -- 9.3.2 T and A -- 9.4 Discussion -- 9.4.1 Critique of Methods -- 9.4.2 Time Course of Respiratory Variants -- 9.4.3 Close Coupling of PvCO 2 and VE -- 9.5 Summary -- References -- Chapter 10: Oxygen Sensitive Synaptic Neurotransmission in Anoxia-Tolerant Turtle Cerebrocortex -- 10.1 Introduction -- 10.2 Oxygen Sensitive Glutamatergic Neurotransmission -- 10.3 Oxygen Sensitive GABAergic Neurotransmission -- References. , Chapter 11: Ion Channel Regulation by the LKB1-AMPK Signalling Pathway: The Key to Carotid Body Activation by Hypoxia and Metabolic Homeostasis at the Whole Body Level -- 11.1 Introduction -- 11.2 K + Channels and the Membrane Hypothesis for O 2 Sensing -- 11.3 Mitochondria and O 2 Sensing -- 11.4 A Set Point for O 2 Sensing Provides the Capacity for Upregulation or Downregulation of Carotid Body Discharge -- 11.5 The Emergence of the LKB1-AMPK Signalling Cascade in O 2 Sensing -- 11.6 AMPK Mediates Type I Cell Activation by Hypoxia -- 11.7 The LKB1-AMPK Signalling Cascade and Carotid Body Activation by Hypoxia -- 11.8 Summary -- References -- Chapter 12: Anoxia Response in Physiological Potassium of the Isolated Inspiratory Center in Calibrated Newborn Rat Brainstem Slices -- 12.1 Introduction -- 12.2 Methods -- 12.3 Results and Discussion -- References -- Chapter 13: Hypoxic Redistribution of Iron and Calcium in the Cat Glomus Cells -- 13.1 Introduction -- 13.2 Methods -- 13.3 Results -- 13.4 Discussion -- References -- Chapter 14: Acute Hypoxia Does Not In uence Intracellular pH in Isolated Rat Carotid Body Type I Cells -- 14.1 Introduction -- 14.2 Methods -- 14.3 Results -- 14.4 Discussion -- References -- Chapter 15: Hydrogen Sul de (H 2 S): A Physiologic Mediator of Carotid Body Response to Hypoxia -- 15.1 Introduction -- 15.2 H 2 S Generating Enzymes in the Carotid Body -- 15.3 Effects of Hypoxia on H 2 S Levels in the Carotid Body -- 15.4 Effects of Inhibition of H 2 S Synthesizing Enzymes on Carotid Body Sensory Response to Hypoxia -- 15.5 Effects of Inhibition of H 2 S Synthesizing Enzymes on Hypoxic Ventilatory Response -- 15.6 Effects of H 2 S Donors on Carotid Body Activity -- 15.7 Cellular Targets of H 2 S Actions in the Carotid Body -- References -- Chapter 16: The Retrotrapezoid Nucleus and Breathing -- 16.1 Introduction. , 16.2 The Retrotrapezoid Nucleus: Definition and Chemosensitivity -- 16.3 How Do RTN Neurons Respond to CO 2 ? -- 16.4 Contribution of the RTN Neurons to the Chemoreflexes -- 16.5 How Do the RTN Neurons Regulate the Respiratory Network and What Else Do They Control? -- 16.6 Pathophysiology -- 16.7 Conclusions -- References -- Chapter 17: The Interaction Between Low Glucose and Hypoxia in the in vitro, Rat Carotid Body -- 17.1 Introduction -- 17.2 Methods -- 17.3 Results -- 17.4 Discussion -- References -- Chapter 18: Do the Carotid Bodies Modulate Hypoglycemic Counterregulation and Baroreflex Control of Blood Pressure In Humans? -- 18.1 Introduction -- 18.2 Methods -- 18.2.1 Subjects and Monitoring -- 18.2.2 Hypoglycemic Clamps -- 18.2.3 Hyperoxia and Normoxia -- 18.2.4 Analytical Methods -- 18.2.5 Data Analysis and Statistics -- 18.3 Results -- 18.3.1 Blood Gases -- 18.3.2 Plasma Glucose, Insulin, and C-Peptide -- 18.3.3 Glucose Infusion Rate -- 18.3.4 Counterregulatory Hormones -- 18.3.5 Blood Pressure -- 18.4 Discussion -- 18.4.1 Mechanisms -- 18.5 Conclusion -- References -- Chapter 19: Shifting from Hypoxia to Hyperoxia to Assess the Peripheral Chemosensory Drive of Ventilation -- 19.1 Introduction -- 19.2 Methods -- 19.3 Results and Discussion -- References -- Chapter 20: CO 2 Signaling in Chemosensory Neuroepithelial Cells of the Zebra sh Gill Filaments: Role of Intracellular Ca 2+ and pH -- 20.1 Introduction -- 20.2 Materials and Methods -- 20.2.1 Cell Isolation -- 20.2.2 Measurement of [Ca 2+ ] i -- 20.2.3 Measurement of pH i -- 20.2.4 General Procedures -- 20.3 Results -- 20.3.1 Effects of Hypercapnic Acidosis on [Ca 2+ ] i -- 20.3.2 Effects of Hypercapnic Acidosis on pH i -- 20.4 Discussion -- References -- Chapter 21: Hyperplasia of Pulmonary Neuroepithelial Bodies (NEB) in Lungs of Prolyl Hydroxylase −1(PHD-1) De cient Mice. , 21.1 Introduction -- 21.2 Methods -- 21.3 Results -- 21.3.1 Immunoperoxidase Method -- 21.3.2 Multilabel Immunofluorescence Method -- 21.4 Discussion -- References -- Chapter 22: Precision-Cut Vibratome Slices Allow Functional Live Cell Imaging of the Pulmonary Neuroepithelial Body Microenvironment in Fetal Mice -- 22.1 Introduction -- 22.2 Methods -- 22.2.1 Animal Preparation -- 22.2.2 Immunohistochemical Staining on Lung Cryosections and Fixed Lung Slices -- 22.2.3 Live Cell Imaging on Fresh Lung Slices -- 22.2.4 Microscopic Data Acquisition and Data Analysis -- 22.3 Results -- 22.4 Discussion -- References -- Chapter 23: Oxygen Sensitivity of Gill Neuroepithelial Cells in the Anoxia-Tolerant Goldfish -- 23.1 Introduction -- 23.2 Methods -- 23.3 Results and Discussion -- References -- Chapter 24: Interaction of Hypoxia and Core Temperature: Potential Role of TRPV1 -- 24.1 Introduction -- 24.2 The TRPV1 Ion Channel and Thermoregulation -- 24.3 Effect of Hypoxia On Thermoregulation -- 24.4 Potential Role of TRPV1 During Hypoxia -- References -- Chapter 25: Neonatal Intermittent Hypoxia Induces Persistent Alteration of Baroreflex in Adult Male Rats -- 25.1 Introduction -- 25.2 Materials and Methods -- 25.3 Results -- 25.4 Discussion -- References -- Chapter 26: LPS-Induced c-Fos Activation in NTS Neurons and Plasmatic Cortisol Increases in Septic Rats Are Suppressed by Bilateral Carotid Chemodenervation -- 26.1 Introduction -- 26.2 Materials and Methods -- 26.3 Results -- 26.4 Discussion -- References -- Chapter 27: Developmental Regulation of Glucosensing in Rat Adrenomedullary Chromaffin Cells: Potential Role of the K ATP Channel -- 27.1 Introduction -- 27.2 Materials and Methods -- 27.2.1 Adrenal Slices -- 27.2.2 Cell Culture -- 27.2.3 Carbon Fiber Amperometry -- 27.2.4 Fura-2 Ratiometric Ca 2+ Imaging -- 27.2.5 Western Immunoblotting. , 27.2.6 Solutions.