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PubMed1984

Perspectives in carotid body research.

This review deals with some basic mechanisms that are operative in carotid body chemoreception. It describes the evolution of concepts and different hypotheses or theories developed to explain possible mechanisms responsible for the onset of sensory discharges in the carotid nerve. Unfortunately, no single hypothesis has been proved beyond doubt, and this may explain their variety. At present, we do not know why this task has been so difficult, although one may think of several possibilities. 1) Carotid body chemoreceptors are anatomically complex being formed by glomus (type I) and sustentacular (type II) cells. Branches of the carotid (sinus) nerve innervate the glomus cells forming sensory synapses oriented in either or both directions and the junction is enveloped by processes of the sustentacular cells. 2) Chemoreceptors are polymodal, since they respond to a variety of natural and chemical stimuli. 3) It is possible that various stimuli may act on different elements of the receptor complex. 4) It is also possible that stimuli may act using different mechanisms. In addition, the multitude of biochemical and biophysical processes (some of them still unknown) operating at different receptor levels has made it very difficult to propose a unified mechanism of action.

Acid-Base Equilibrium↗
PubMedDate not supplied

[Arterial chemoreceptors: cellular and molecular mechanisms in the adaptative and homeostatic function of the carotid body].

The carotid body is a sensory chemoreceptor organ located in the vicinity of the carotid bifurcation. Structurally it is composed of cell clusters formed by chemoreceptor and supporting cells. The sensory nerve endings of the carotid sinus nerve penetrate the clusters to synapse with chemoreceptor cells. The carotid body plays an important role in the control of ventilation during hypoxia, hypercapnia and acidosis. Hypoxia and other natural stimuli are detected by chemoreceptor cells which upon stimulation increase their rate of release of neurotransmitters. Neurotransmitters in turn increase the action potential frequency in the carotid sinus nerve which via its central projections to the brainstem activates ventilation. This review is devoted to the cellular aspects of the function of this chemoreceptor organ. From a brief description of the complex structure of the carotid body, we go to present a summary of the main prevailing theories concerning the transduction mechanisms for hypoxic and acidic/hypercapnic stimuli, with special emphasis on the electrical properties of cultured chemoreceptors cells. A special attention is provided to the possible significance of reactive oxygen species as mediators of the hypoxic transduction cascade. The neurotransmission between chemoreceptor cells and the sensory nerve endings is also covered in certain detail. After a brief historical presentation of the theories of communication between these two structures, we examine, following the classical criteria of neurotransmission, the functional significance of acetylcholine, dopamine, substance P and other neurotransmitters known to be present in chemoreceptor cells.

Adaptation, Biological↗
PubMed2000

Regulation of Shaker-type potassium channels by hypoxia. Oxygen-sensitive K+ channels in PC12 cells.

Little is known about the molecular composition of the O2-sensitive K+ (Ko2) channels. The possibility that these channels belong to the Shaker subfamily (Kv1) of voltage-dependent K+ (Kv) channels has been raised in pulmonary artery (PA) smooth muscle cells. Numerous findings suggest that the Ko2 channel in PC12 cells is a Kv1 channel, formed by the Kv1.2 alpha subunit. The Ko2 channel in PC12 cells is a slow-inactivating voltage-dependent K+ channel of 20 pS conductance. Other Kv channels, also expressed in PC12 cells, are not inhibited by hypoxia. Selective up-regulation by chronic hypoxia of the Kv1.2 alpha subunit expression correlates with an increase O2-sensitivity of the K+ current. Other Kv1 alpha subunit genes encoding slow-inactivating Kv channels, such as Kv1.3, Kv2.1, Kv3.1 and Kv3.2 are not modulated by chronic hypoxia. The Ko2 current in PC12 cells is blocked by 5 mM externally applied tetraethylammonium chloride (TEA) and by charydbotoxin (CTX). The responses of the Kv1.2 K+ channel to hypoxia have been studied in the Xenopus oocytes and compared to those of Kv2.1, also proposed as Ko2 channel in PA smooth muscle cells. Two-electrode voltage clamp experiments show that hypoxia induces inhibition of K+ current amplitude only in oocytes injected with Kv1.2 cRNA. These data indicate that Kv1.2 K+ channels are inhibited by hypoxia.

Animals↗
PubMed1979

APUD-type recepto-secretory cells in the chicken lung.

The epithelium of the intrapulmonary airways of the chicken lung has been studied by fluorescence and electron microscopy. Numerous intensely yellow-fluorescent cells occur in the epithelium of the primary and secondary bronchi. The cell cytoplasm contains characteristic granular vesicles with an electron-dense central core. The vesicles react positively to chromaffin and argentaffin treatment, indicating that they are possible storage sites for amines. Synapse-like junctions occur between the granular cells and the intraepithelial nerve endings, filled with numerous mitochondria, suggesting that these granular cells may have a dual function as both receptor and endocrine cell.

APUD Cells↗
PubMed1991

Taste cells in the gut and on the tongue. Their common, paraneuronal features.

Chemoreception of foodstuff in the gut is performed by endocrine cells dispersed in the gut epithelium. They are bipolar cells extending an apical process to the gut lumen and releasing their messenger substances from the cell base in response to the apical stimuli. The cells share cell-biological features with neurons and are classified as paraneurons. Noteworthy, the gut paraneurons do not seem to be stimulated by monosodium glutamate (MSG) as our dog experiment indicates. Administration of 50 mM MSG into the duodenal loop of anesthetized dogs did not cause changes in the volume and protein output in the pancreatic juice. The gustatory cells in the taste bud show essentially the same structure and function as the gut endocrine cells. A single gustatory cell type (type III) seems to receive different chemical stimuli, whereas different endocrine cell types in the gut react to different stimuli. The gustatory cells possess numerous peptidergic-type granules besides synapse-associated small clear vesicles. The former granules, in the guinea pig and dog, are abundant in the cytoplasm, giving an endocrine-like appearance to the cell. Peptidic signal substances contained in the granules remain to be identified. Comparison of the gustatory cells in the taste bud with the endocrine cells in the gut and with other paraneurons may put into front certain hitherto unexplored structures and functions of the cells.

Animals↗
PubMed1987

Time-dependent ligand current into a single cell performing chemoreception.

We determine the ligand current into a single spherical cell which carries a large number of receptors on its surface. Initially, this cell is placed into a medium which contains ligands at uniform concentration. The time-dependent ligand distribution is calculated, from which the time-dependent ligand current into the cell is derived. If the ligand concentration is kept constant at distances comparable to the radius of the cell the stationary state sets in at times comparable to the T1 necessary for ligands to travel a distance of the order of the radius of the cell. If the ligand concentration is kept constant at infinity the stationary state sets in at a time which is about 1000T1 for typical values of the parameters.

Cell Physiological Phenomena↗
PubMedDate not supplied

Coding in taste receptor cells. The early years of intracellular recordings.

In the gustatory system, the mechanism of coding-the process of relaying the identity and intensity of the stimulus to the central nervous system-begins with the taste receptor cells. Ironically, although these are the first cells of the gustatory system to contact stimuli, they were the last from which neurophysiological recordings were obtained. How taste receptor cells decipher stimulus identity remains the subject of active research; its origins began with a series of intracellular studies. Prior to the first intracellular recording, it was unknown if taste receptor cells would be specialists, responding to only a single class of taste stimulus, or generalists, responding to multiple stimuli. The first reports established several major aspects of these cells' physiology. Taste receptor cells have varying response profiles to basic stimuli; they have obvious conductance changes during stimulation; they have low resting potentials. It became evident that multiple transduction schemes must underlie these responses, although the identity of these transduction schemes remained elusive. Additionally, these early recordings missed a major phenomenon-the presence of regenerative electrical events (i.e., the action potential) was not observed due to the low input resistance that accompanied this technique. Although intracellular recordings are essentially no longer used to study taste receptor cells, replaced by the superior method of patch-clamp recording, these early articles provided key insights into the then unknown electrical responses of taste receptor cells.

Animals↗
PubMed1998

Hyperpolarization-activated inward currents contribute to spontaneous electrical activity and CO2/H+ sensitivity of cultivated neurons of fetal rat medulla.

Neurons growing out from cultivated fetal medullary slices that exhibited spontaneous electrical activity after blockade of synaptic transmission were investigated by the patch-clamp technique for their response to decreases in the extracellular pH. Increases in the [H+], induced by increases in pCO2, resulted in a decrease in spike frequency associated with a decrease in the rate of depolarization preceding each action potential. The type of ion channel, contributing to interspike depolarization, and which may therefore be the site of CO2/H+ action, was identified by application of agents that inhibited the hyperpolarization-activated cation, IH, channel (Cs+ and ZD7288). Application of Cs+ and ZD7288 slightly hyperpolarized the cell membrane, decreased the interspike slope and inhibited CO2/H+-induced modulations of spike frequency in one group of CO2-inhibited medullary neurons, suggesting that IH contributes to spontaneous neuronal activity and to CO2/H+-sensitivity. CO2/H+ effects on IH were further confirmed in voltage-clamp experiments. Increasing the bath CO2 from 2% to 9% reduced the IH amplitude, shifted the mean EH from -54 to -60 mV, lengthened the voltage-dependent delay of current activation and increased the time-constants of activation at all potentials studied. It is concluded that depolarizing inward currents through IH channels participate in the gradual ramp-like change in membrane potential which depolarizes the cell up to the threshold of Na+ spike generation. CO2/H+-induced inhibition of IH reduces the contribution of this ion current to the interspike depolarization and accounts for the CO2/H+-induced decrease in spike frequency in one type of CO2/H+-inhibited medullary cells.

Action Potentials↗
PubMed2003

Protons open acid-sensing ion channels by catalyzing relief of Ca2+ blockade.

Acid-sensing ion channels (ASICs) open when extracellular pH drops and they are enhanced by lactate, making them specialized for detecting lactic acidosis. Highly expressed on cardiac nociceptors and some other sensory neurons, ASICs may help trigger pain caused by tissue ischemia. We report that H(+) opens ASIC3 by speeding release of Ca(2+) from a high-affinity binding site (K(Ca) = 150 nM) on the extracellular side of the pore. The bound Ca(2+) blocks permeation and the channel conducts when multiple H(+) ions relieve this block. Activation through Ca(2+) explains sensitivity to lactate, which decreases extracellular [Ca(2+)], and it may prove relevant in CNS pathologies (stroke, seizure) that simultaneously drop pH and Ca(2+).

Acid Sensing Ion Channels↗
PubMed1979

Attractants and repellents influence methylation and demethylation of methyl-accepting chemotaxis proteins in an extract of Escherichia coli.

During bacterial chemotaxis, attractants and repellents alter the methylation levels of the methyl-accepting chemotaxis proteins (MCPs). These methylation levels represent a balance between two enzymatic processes: methylation and demethylation. In vivo experiments previously have shown that chemoeffectors influence the demethylation process; effects on the methylation system have not been reported. Here we show that in a cell-free extract of Escherichia coli both methylation and demethylation of the MCPs are affected by attractants and repellents. Attractants enhance methylation and inhibit demethylation. Repellents inhibit methylation and stimulate demethylation. The cell-free system provides an opportunity for further study of the mechanisms by which attractants and repellents influence the levels of methylation of the MCPs.

Bacterial Proteins↗
PubMed1997

Guanylyl cyclase expression in specific sensory neurons: a new family of chemosensory receptors.

A guanylyl cyclase (GC-D) was recently shown to be expressed in a subclass of neurons within the neuroepithelim of the rat, but given that only a single cyclase was discovered, whether it represents an odorant/pheromone receptor as has been suggested for the large family of seven-transmembrane receptors remains unclear. Through cloning and expression of cDNA we now demonstrate that at least 29 genomic or cDNA sequences found in Caenorhabditis elegans represent guanylyl cyclases. Many of the membrane forms retain cysteine residues conserved within the extracellular, ligand-binding domain of known cyclase receptors. Of eight orphan cyclase receptor::GFP (green fluroescence protein) fusion constructs for which signals were obtained, all were expressed in specific sensory neurons. Furthermore, a cyclase/GFP fusion protein (GCY-10/GFP) was principally expressed in the sensory cilium, suggesting these cyclases function as primary chemosensory receptors. For the first time, we also found that chemosensory neurons (ASE), known to be bilaterally symmetric, demonstrate absolute right or left sidedness with respect to the expression of three different cyclases. Thus, the guanylyl cyclases represent an unexpectedly large and new family of sensory neuron receptors that may complement the 7-transmembrane family of odorant/pheromone receptors.

Animals↗