ion channels - Oboulo.com

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biology

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26/11/2007

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Summary

Classes of Neurotransmitters Much of the information transfer between neurons in the CNS occurs via chemical synapses. These synapses use a variety of messengers (neurotransmitters) that are released in a Ca2+-dependent fashion from presynaptic terminals and act on specific protein receptors to produce biochemical and excitability changes in the receiving cell. There are two primary groups of neurotransmitters—low–molecular-weight amines and neuroactive peptides. These agents act on two classes of receptors, ligand-gated ion channels, at which the binding of the transmitter directly opens ion channels in the membrane, and G protein coupled receptors. The activated G protein then acts on ion channels or alters biochemical second-messenger systems. Physiologists classify synaptic transmission according to the speed of transmission (fast or slow) and according to the nature of the response (excitatory or inhibitory).

Currently, there are nine low–molecular-weight amines that serve as neurotransmitters.
Conductance Mechanisms Underlying Neurotransmitter Actions
Structure of Neurotransmitter Receptors Considerable information now exists about the primary structure of neurotransmitter receptors.
The ligand-gated ion channels gated by extracellular ATP (called P2X receptors) are exceptions to the scheme described above and have structures more typical of the inwardly rectifying K+ channels.
G-protein coupled receptors have a distinctly different structure from the ligand-gated ion channels.

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biology

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26/11/2007

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Structure and Function of Voltage-Gated Ion Channels Voltage-gated ion channels allow the flow of ions in response to changes in membrane voltage and are key elements in neuronal excitation and inhibition. Although ion channels can usually pass more than a single type of ion, voltage-gated channels are named according to the predominant ion that flows when the channel is open. Ion channels that are selective for Na+, K+, Ca2+, or Cl– have been described in neuronal membranes. Certain ion channels that are gated directly by chemical neurotransmitters such as glutamate and acetylcholine are selective for Na+, K+, and Ca2+ but exclude Cl– and are called nonselective cationic channels.

Sodium (Na+) Channels Na+ channels are primarily responsible for the fast upstroke of action potentials, although in some neurons Na+ channels also contribute to lower-level depolarizations and pacemaker firing.
Relations between primary protein structure and ion channel function in Na+ channels have been examined using mutations of specific amino acid residues.
The net effect is similar to the scorpion toxins. Finally, certain local anesthetic drugs, including lidocaine and procaine, block Na+ channels by binding reversibly to sites within the hydrophobic regions of the ion channel.
Delayed-rectifier channels open slowly and show little inactivation during prolonged depolarizations.
M channels represent a class of K+ channels that are activated in a time- and voltage-dependent fashion but are blocked by the neurotransmitter, acetylcholine, acting at muscarinic receptors.
KATP channels exist in the CNS and appear to be involved in regulating the release of certain neurotransmitters and perhaps in determining the response of some neurons to changes in intracellular energy levels.
Calcium (Ca2+) Channels Because Ca2+ is involved in numerous cellular events including enzyme activation, gene expression, and neurotransmitter release, the regulation of intracellular Ca2+ levels is of major importance to neurons.
Most structural information about Ca2+ channels comes from skeletal muscle HVA Ca2+ channels.

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biology

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26/11/2007

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Resting Membrane Potential In nerve cells, potassium ions (K+) are at higher concentration inside the membrane than outside whereas the opposite is true for sodium (Na+), calcium (Ca2+), and chloride (Cl–) ions (Fig. 1.9-1). The bulk solutions on either side of the membrane are electrically neutral, with most of the intracellular negative charge being contributed by large organic anions (acids and proteins). The differential distribution of ions across neuronal membranes results in part from the action of membrane pumps that use energy from adenosine triphosphate (ATP) to drive ions against a concentration gradient into or out of the cell. The best characterized pump is the Na+-K+ adenosine triphosphatase (ATPase) that transports 3 Na+ out of and 2 K+ into the cell during each cycle. Because an unequal amount of charge is moved during each cycle, the pump is electrogenic and produces an electrochemical potential across the membrane that makes the inside of the membrane negative with respect to the outside. Na+-K+ ATPase activity is a major contributor to brain energy utilization, with as much as 40 percent of brain oxygen consumption resulting from pump activity required to reestablish ionic homeostasis following action potential firing and synaptic transmission. The cardiac glycosides digoxin (Lanoxin) and ouabain are effective inhibitors of Na+-K+ ATPase in the heart and improve myocardial contractility by depolarizing cardiac myocytes and increasing intracellular Ca2+.

At rest, neuronal membranes are permeable to K+ and Cl– and to a lesser extent to Na+, partly because of the flow of ions through nongated leakage channels.
For each ion in solution there is a specific membrane potential at which the opposing forces of the electrical gradient and concentration gradient are balanced.
Because ions do not directly penetrate the lipid membrane but rather flow through ion channels, the ion channels can be thought of as variable resistors.
Active Membrane Properties: Action Potentials Changes in membrane potential have important effects on excitability because certain ion channels are activated (gated) by voltage changes.
Many axons are encased in myelin sheaths that allow them to send action potentials over longer distances.

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biology

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26/11/2007

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In its simplest form, the postsynaptic response to neurotransmitter release can be mediated by a single protein complex. For example, nicotinic acetylcholine receptors are self-contained stimulus-response modules that both detect a stimulus, acetylcholine, and generate a response, passage of ion currents. In a similar vein, other members of this superfamily of ionotropic receptors, including g-aminobutyric acid (GABA) and glutamate receptors, have the ability to function in a manner that is independent of the intracellular signaling pathways discussed. Thus, in contrast to growth factor or G-protein–coupled receptors, which often recruit elaborate cascades to elicit a response, the simplicity of self-sufficient ionotropic receptor complexes represents an optimal design for achieving reliability, precision, and speed. However, this view of ionotropic receptors as insulated from their social environment has had to be abandoned in the face of overwhelming evidence that this class of receptors is dynamically regulated by intraneuronal signaling pathways. Although these receptors do not rely on intraneuronal signaling pathways to operate ion channels, because these channels are an intrinsic feature of the receptor complex the linkage between ligand binding and ion channel gating is nevertheless subject to regulation by the network of intraneuronal signaling pathways just described. For example, phosphorylation of the GABA or glutamate receptors modulates their response to ligand exposure.

Long-Term Depression The principle that ion channels are regulated by second messenger pathways is of central importance in considering how neuronal responses are altered by experience.
Long-Term Potentiation The notion that coactivation of multiple second messenger pathways can have a qualitatively different impact than any one individually is also borne out in another well-known model of synaptic plasticity, long-term potentiation.
This unusual property of NMDA receptors provides a molecular mechanism for conferring associative properties on long-term potentiation.
Role of Phosphorylation The associative property of this model of synaptic plasticity has focused attention on deciphering the intraneuronal signaling pathways that mediate the long-term change in synaptic transmission triggered by NMDA receptor stimulation.
Actions of Psychotropic Drugs In addition to providing insight into the molecular mechanism underlying synaptic plasticity, studies of intraneuronal signaling pathways are also directly relevant to deciphering the mode of action of psychotropic drugs.
Evidence supporting this theory has been provided by recent studies demonstrating that opiate withdrawal is attenuated in transgenic animals that are deficient in CREB.

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medical studies

case study

date published

23/10/2007

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Summary

One of the most important organs in the body is the heart. Of course, this organ is of great importance not only in humans but in all vertebrates. Blood, which carries nutrients, oxygen, and wastes from organ to organ within the body is pumped by the heart. Without the heart’s pumping action, blood would simply remain stagnant within the vessels of the body, and any vertebrate in this condition would die off very quickly.

While the heart is essential to all vertebrates alike, it is important to note that there are some stark distinctions between the hearts of different vertebrates.
Although the heart is able to initiate its own action potential and make itself beat, there are sympathetic and parasympathetic neurons that innervate it.
As compared to the control, adding epinephrine sped up heart rate but, according to the readings, decreased contractile strength.

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biology

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26/11/2007

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Prior to delineating the organization of specific intraneuronal signaling pathways, it is important to consider, in general terms, their role in helping neurons interpret and respond to the barrage of afferent stimulation impinging on them continuously. From an evolutionary perspective, second messenger systems predate neurotransmitters and neurotrophins, examples of first messengers detected by cell surface receptors. Before the advent of neurotransmitters, prokaryotic organisms relied on cyclic adenosine monophosphate (cAMP) and other intracellular signaling pathways to coordinate diverse responses located in disparate parts of these unicellular organisms to changes in ambient nutrients or conditions. Neurotransmitters and neurotrophins have evolved subsequently to take advantage of these internal signaling pathways that have undergone a parallel growth process.

Intraneuronal signaling pathways do more than merely enlarge the sphere of influence of afferent stimuli beyond the local environment of the cell surface receptor.
Although the overwhelming majority of psychiatric drugs target extracellular receptors or uptake sites, the explosion of information on intraneuronal signaling pathways suggests that these may represent suitable drug targets.
Psychiatrists have long been taught that a true understanding of normal and abnormal behavior requires an appreciation of the interplay of forces lurking beneath the surface.
Neurotransmitter receptors may couple to adenylate cyclase via different classes of G proteins, referred to as Gs or Gi, depending on whether they stimulate or inhibit cyclic AMP formation.
Cyclic GMP Besides cyclic AMP, another cyclic nucleotide, cyclic guanosine monophosphate (GMP) has been identified as a second messenger regulated by neurotransmitter receptor stimulation.
Because the effects of cAMP are mediated to a large extent via activation of a kinase, it was generally assumed that each of these second messengers acted in a similar fashion.
However, this view has been challenged recently in light of animal studies demonstrating that inositol levels in brain are unaffected by lithium concentrations within its therapeutic range.
These alternate arrangements emphasize the notion that intracellular signaling cascades have evolved in ways that heighten their versatility, with each of the components having multiple signaling capacities.
Another family of tyrosine kinases has been identified that differs from the receptor tyrosine kinases in that it contains only the cytoplasmic domain.
Cross-Talk Among Signaling Pathways The organization of intraneuronal signaling pathways allows for a high degree of interaction or cross-talk among pathways

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3 word format

Language : english

biology

school essay

date published

17/09/2007

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The human body is a fascinating array of mechanisms, each perfectly sculpted to satisfy its role in the ever changing needs of our physiology. The various systems within us each rely on impulses, sent via the central or peripheral nervous systems, to coordinate everything from breathing to walking to thinking. These messages, sent throughout the entire body and relayed through neurons, consisting of axons and dendrites, are just as intricate as the systems they support.

The human body is a fascinating array of mechanisms, each perfectly sculpted to satisfy its role in the ever changing needs of our physiology
The voltage gated potassium channel through which K+ ions diffuse is shaped somewhat like an 'upside down teepee?.
Legend: Two of the helical subunits of a voltage gated potassium channel, along with carbonyl binding sites at the top, which is the narrowest region of the channel
The voltage sensor paddles hold four positive charges, making the total sixteen, which slide almost all the way through the fluid membrane.

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6 word format

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psychology

research papers

date published

13/11/2007

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Ultimately the effects of monoamines on CNS function and behavior depend upon their interactions with receptor molecules. The binding of monoamines to these plasma membrane proteins initiates a series of intracellular events that modulate neuronal excitability. Unlike the transporters, multiple receptor subtypes exist for each monoamine transmitter. The initial classification of many receptor subtypes was based on radioligand binding studies. Receptor binding sites were identified on the basis of the rank order of binding affinities for a number of agonist and antagonist compounds. More recently, the molecular cloning of monoamine receptors has confirmed that many of the sites initially defined by these binding studies did indeed correspond to distinct receptor proteins encoded by unique genes. Molecular cloning has also led to the identification of previously unknown receptors, and to the introduction of powerful tools to characterize receptor structure and function.

Neurotransmitter receptors produce intracellular effects by one of two basic mechanisms:
In the wake of the recent proliferation of known receptors subtypes, much work needs to be done to determine the functional roles of individual receptors.
The 5-HT1 receptors comprise the largest serotonin receptor subfamily, with human subtypes designated:
At least three receptor subtypes mediate the effects previously attributed to a single 5HT2 receptor subtype.
The 5-HT3 receptor is unique among monoaminergic receptors in its membership within the ligand-gated ion channel superfamily.
The D1 receptor was initially distinguished from the D2 subtype by its high affinity for the antagonist SCH 23390 and its relatively low affinity for butyrophenones such as haloperidol
The dopamine D2 receptor was initially distinguished from the D1 receptor on the basis of its high affinity for butyrophenones.
The D3 and D4 receptors are considered to be D2-like on the basis of similarities in their gene structures, sequence homologies, and pharmacology.
Like the a-adrenergic receptors described, b-adrenergic receptors (designated including subtypes b1, b2, and b3) are found both in the brain and in many peripheral tissues.
Unlike H1 and H2 histamine receptors, H3 receptors are located presynaptically on axon terminals.
Within the human brain, nicotinic acetylcholine receptors are found at highest densities within the hippocampal formation, neocortex, substantia nigra, ventral tegmental area, dorsal raphe nucleus, periaqueductal gray, and the basal forebrain cholinergic complex.

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5 word format

Language : english

psychology

presentation

date published

26/11/2007

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Summary

GABAA Receptor The GABAA receptor is a member of the superfamily of ligand-activated ion channels in the cell membrane. GABA type A (GABAA) receptors are most closely related to strychnine-sensitive glycine receptors, more distantly related to acetylcholine nicotonic receptors and serotonin 5-hydroxytryptamine (5-HT) [5-HT] type receptors, and even more distantly related to glutamate ionotropic receptors (AMPA and kainate receptors and NMDA receptors). GABAA receptors are heteropentameric protein complexes, which when activated undergo a series of conformational changes that form an open channel (pore) selectively permeable to anions, specifically chlorine anion (Cl–) and to a lesser degree (HCO–3). Receptor activation normally results in an influx of Cl– which rapidly and transiently hyperpolarizes the membrane, a process generally referred to as the generation of an inhibitory postsynaptic potential. The increase in Cl– flux also decreases the resistance of the membrane, which acts as a shunt to impede the ability of depolarizing excitatory postsynaptic potentials to elicit action potentials (nerve impulses).

GABAA receptors are heteromeric in that the receptor can comprise at least four types of subunit proteins, termed a, b, g, and d. It is pentameric in that each receptor has a total of five proteins
A variety of pharmacological agents can influence the activity of GABAA receptors
GABAB Receptors The metabotropic GABAB receptors are a member of the superfamily of G-protein-coupled receptors expressed in the cell membrane.
However, it is likely that a breakdown in the regulation of glutamate is a major factor.
Epilepsy Epilepsy is a group of neurological disorders characterized by spontaneous recurrent seizures.
Although many neurobiological factors may contribute to seizure formation, a prominent feature of most seizures is an abnormal and excessive firing of glutamatergic neural pathways.
Kindling, which is a gradual induction of a hyperexcitable neuronal state, can occur by focal repetitive subconvulsive stimulation of the hippocampus, amygdala, or some other brain areas.
Neuropathic Pain Activation of afferent C fibers with nociceptive stimuli produces pain sensations that are enhanced during pathological conditions.
A pregnane-derived synthetic neurosteroid is in clinical trials for treatment of epilepsy.
Substance Abuse Ethanol enhances GABA receptor function in some in vitro preparations potentially via a protein-binding site.

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5 word format

Language : english

biology

presentation

date published

18/09/2007

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