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9 Cards in this Set
- Front
- Back
- 3rd side (hint)
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What are the possible effects of ligand binding a ligand-gated channel?
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1) Fast response - The extracellular signal can act directly at the channel protein and change its conformation. These signals act very rapidly, on the millisecond scale. Among the proteins that respond in this way are the ligand-gated channels, also called ionotropic receptors. These channels play important roles in signaling between neurons, and in transmission from neurons to muscle skeletal muscle cells. The ligand-gated channels are the topic of this lecture.
2) Slow response - The extracellular signal can generate a second messenger in the target cell, which in turn can affect the activity of specific channels. These responses, which are considerably slower than those mediated by the ligand-gated channels, will be discussed in our next lecture. |
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What are two categories of Ligand-Gated channels? Examples of each?
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1. Cys-Loop Channels
e.g. nicotinicacetylcholine receptor e.g. GABA receptor 2. Glutamate receptors e.g. AMPA-type e.g. NMDA-type |
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What are Cys-Loop receptors? What ions do they channel?
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The channels of Cys-loop receptors are selective for either cations or anions, but otherwise are relatively non-discriminating. Selectivity for cations is conferred by rings of negatively charged residues lining outer regions of the pore, on both the extracellular and cytoplasmic sides. Channels are permeable primarily to Na+ (inward) and K+ (outward), but they also allow Ca2+
and Mg2+ ions to move through. - The reversal potential is about 0 mV. - The pore is large enough to conduct ions with their hydration shells largely intact. How are nAChRs gated? |
Gating mechanism: - In the absence of acetylcholine, each of the M2 helices has a hydrophobic kink directed into the
pore, and together they block the channel. When both binding sites are occupied by acetylcholine, the M2 helices twist away from the center of the pore, permitting current flow. |
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Describe GABA-A receptors.
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The GABA-A receptor is a ligand-gated channel.
Has binding sites for the neurotransmitter γ-aminobutyric acid (GABA) - Mediates fast inhibitory transmission in the brain (closely related Cys-loop receptors that respond to glycine serve this function in the spinal cord) What ion is GABA selective for? How does it accomplish this? |
- Anion (Cl-)-selective, with a reversal potential of about -80 mV - Selection is accomplished by positively charged residues lining the pore (instead of the
negatively-charged rings of the cation-selective nAChR channel) |
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Describe glutamate receptors, what types there are.
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Receptors that are activated by glutamate. There are two types that are selective for different ions:
- The AMPA-type is selective for Na+ and K+ - Reversal potential is ~ 0 mV - The NMDA-type is additionally permeable to Ca2+ - Reversal potential is ~ +20 mV What is needed for activation of each? |
- For both types, opening requires the binding of the neurotransmitter glutamate - Opening of NMDA-type additionally requires the binding of extracellular glycine. - The NMDA-type channel is blocked by an extracellular Mg2+ ion at the resting Vm. The Mg2+ is
expelled upon strong membrane depolarization AMPA receptors get activated sooner and depolarize the membrane; if depolarized enough, then NMDA receptors are activated. NMDA = helps form memories |
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What are signaling pathways involving calcium release from internal stores?
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The IP3 receptor predominates in the ER, while the Ca2+–responsive receptor (the ryanodine receptor) is found in both ER and SR.
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What is the effect of PIP2 depletion on K+ channel inactivation?
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PIP2 depletion increases K+ inactivation (because the negatively charged inositol groups are removed, removing interference from the positively charged "Ball" N-terminus blocking group, allowing inactivation)
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Describe the ATP-sensitive K+ channel KATP
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The pore region of KATP is contributed by a weakly inward rectifying channel, Kir6.2, which is directly inhibited by ATP. Surrounding Kir6.2 are four identical subunits of the ABC-type protein SUR1 (sulfonylurea receptor 1), each with two nucleotide-binding domains (NBDs). Depolarizes when glucose (ATP/ADP) is high to release insulin, does not when blood glucose is low.
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What are SUR1 and Kir6.2?
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ADP, by binding to the NBDs of SUR1, indirectly opens the channel of Kir6.2. Thus, the KATP octamer is highly responsive to the ratio of ATP:ADP. The pore region of KATP is contributed by a weakly inward rectifying channel, Kir6.2, which is directly inhibited by ATP
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