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22 Cards in this Set
- Front
- Back
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GABAaR is what |
a chloride conducting ligand gated ion channel; gamma aminobutyric acid or GABA is the major inhibitory neurotransmitter in the CNS and the GABAa receptor is a major target for many important drugs (ex. anesthetics, benzodiazepines (anxiety disorders), barbiturates (anticonvulsant or antiseizure drugs), and alcohol) |
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ligand gated ion channels: open in response to |
open in response to the biding of neurotransmitters such as acetylcholine or gamma aminobutyric acid |
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voltage gated ion channels: open in response to |
a change in the membrane potential; (another lecture will talk about the anticonvulsants phenytoin and carbazepine which are used to treat epilepsy these channels will be important) |
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other ion channels open in response to what other things |
intracellular signals; mechanical stimuli, pH, or temp |
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active transporters or ion pumps do what |
are membrane proteins that expend energy to transport ions across the membrane to produce and maintain ion concentration gradients; Na, K ATPase is the most important one of these and it utilizes energy derived form the hydrolysis of ATP to transport sodium ions to one side of the membrane and K ions to the other; other active transporters establish concentration gradients for ions such as chloride, calcium, and protons |
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ion exchangers and co transporters so what |
use these gradients to move other ions or molecules; ex. co transporters that use the movement of sodium down its concentration to move neurotransmitters like dopamine (DAT), serotonin (SERT), and norepinephrine (NET) from synaptic cleft back into the presynaptic terminal; these will be important in the lecture about Prozac and Bupropion which treat depression |
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patch clamp method |
capable of measuring the currents flowing through single channels; use a glass pipette with a very small opening and connect it to a tiny area or patch of a neuronal cell membrane; after the application of a small amount of suction the seal between the pipette and the membrane thus all the ions that flow when a single ion channel is open must flow into the pipette and the resulting current can be recorded with an ultra sensitive electronic amplifier |
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the opening and closing of Na channels |
are voltage dependent; if you apply different membrane potentials and then sum up the number of open channels you see a nice Boltzmann relationship between the membrane potential and the probability of channel opening |
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the opening and closing of K channels |
K flows form the intracellular space outwards, down the concentration gradient; K channels, in contrast to the Na channels, are not inactivated and so the channel remains open as long as the membrane remains depolarized but the channel closes when the membrane potential is returned to normal; channel opening is voltage dependent |
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functional states of channels |
membrane depolarization is sensed by a voltage sensor in the Na channel which then leads to opening of the ion channel pore, Na ions flow outward and then an inactivating domain then closes the channel; these functional states will be important in the lecture about anticonvulsant drugs that treat seizure/epilepsy |
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different types of voltage gated ion channels |
differ slightly in their structure, their functional properties, and in their distribution in specific tissues or regions of the brain; there are Na channels that inactivated very rapidly, such as those in the squid axon, and there are those that do not inactivate and which give rise to prolonged action potentials; these particular Na channels are particularly sensitive to local anesthetics such as benzocaine and lidocaine |
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different types of Ca channels |
voltage gated Ca channels; in many neurons Ca channels can control the shape of action potentials generated by Na channels and therefore modulate the electrical signaling; ex. T type VG Ca channels in the thalamus help establish a 3 hertz spike and wave rhythm seen in absence or petit mal seizures; the anti seizure drug ethosauximide stabilizes the inactive state of these particular Ca channels and inhibits absence seizures; ca channels regulate an enormous range of biochemical processes within cells including the release of neurotransmitters from the presynaptic membrane |
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different types of K channels |
the largest and most diverse class of voltage gated ion channels; 4 groups |
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the 4 groups of K channels |
some like the Kv2.1 channel show very little inactivation; some like the Kv4.1 channel inactivated within 10s of milliseconds; the HERG channel inactivates so rapidly those current flows only when the inactivation is removed at the end of a repolarization; inward rectifier type K channels allow K to flow at hyperpolarized membRane potentials rather than at depolarizing potentials and the K currents flowing through these channels are an important COMPONENT OF THE RESTING MEMBRANE POTENTIAL |
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different types of Cl channels |
again many and all over the body |
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ligand gated versus voltage gated chennels |
ligand gated channels typically allow for the passage of more than one ion, for ex both Na and K and in some cases Ca ions can pass through the acetylcholine receptor |
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ligand gated ion channels: what is its make up |
tetrameric pentameric channels with different subunit combos provides for a tremendous diversity in function which is also relevant to drug interactions and side effects |
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other ligand gated ion channels are opened by |
chemical signals form within the cytoplasm such as Ca as well as cyclic nucleotides; these types of channels play an important role in sensory transduction |
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primitive bacterial K channel composition |
4 identicle subunits arranged together as a tetramerl each subunit contains 2 segments which traverse the lipid bilayer in an alpha-helical secondary structure; the association of these membrane spanning segments forms a tunnel through the lipid bilayer called a pore through which the K ion traverses; at the outside mouth of the channel were the K ions enter these is a restriction in the channel pore that is formed by what is called the selectivity filter domain; here the diameter of the pore is just narrow enough to allow a single K ion to pass through; the pore is too small to allow a larger Cs ion to pass through but is too big to interact with a Na ion and allow it to pass through; hence this region determines which ions can pass through the channel; by adding other structural domains it is believed that voltage activation and inactivation are added and auxillary subunits further alter the function; also by making subtle changes in the structure of the selectivity filter the ion selectivity can be changed from K to Na or to Ca |
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voltage sensor |
a special property of voltage gated ion channels is a sensor that detects changes in the membrane potential and which then opens the channel; this sensory is a alpha helical transmembrane segment which contains positive charges along the length of it; depolarization pushes the sensor outward while hyperpolarization pulls the sensor inward; the movement of the sensor exert force on the helical linkers connecting the sensors to the channel pore pulling it open or pushing it closed |
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co transporters do what |
remove the neurotransmitters dopamine (DAT), serotonin (SERT), and norepinephrine (NET) form the synapse in exchange for Na moving down its concentration gradient |
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ouabain does what |
inhibits the Na/K pump; bad |
