Exam 1 - Neurotransmitters and Receptors Flashcards

1
Q

what are the criteria for neurotransmitters?

A
  • must be present in presynaptic neuron
  • must be released in response to presynaptic depolarization, and this release is dependent on Ca2+ influx into the presynaptic terminal
  • specific receptors that recognize it must be present on the post-synaptic cell
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2
Q

describe ionotropic receptors

A
  • ligand-gated
  • directly linked to ion channel
  • 2 fxnal domains: 1 extracellular to bind neurotransmitter + 1 transmembrane as channel
  • 4 or 5 protein subunits
  • produce PSPs w/i 1-2 ms of presynaptic AP (fast)
  • neurotransmitter binds receptor and causes ion channel to open
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3
Q

describe metabotropic receptors

A
  • GPCRs
  • receptor and ion channel physically separate
  • channel activated by intermediate G-proteins and second messengers
  • receptor = monomeric protein w/ 2 domains: 1 extracellular to bind neurotransmitter + 1 intracellular to bind G-protein
  • 7 transmembrane segments
  • produce PSPs w/i ms to minutes after AP (slow)
  • direct or indirect interaction with ion channel to open it
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4
Q

describe nicotinic acetylcholine receptor (nAChR) structure

A

-ionotropic receptor
-funnel-shaped integral membrane protein of 5 subunits
-large extracellular portion
-each subunit has:
-long, hydrophilic N-terminal domain
-3 hydrophobic segments in membrane (TM 1,2,3)
-stretch of hydrophilic domain
-fourth hydrophobic domain in membrane near C-
terminus (TM4)
-ACh binding site near disulfide bond in N-term domain
-TM2 segment in each subunit lines pore

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5
Q

describe how nAChR is opened

A

ACh binding causes TM2 segments to rotate about 90 degrees, allowing ions to pass through the pore

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6
Q

what does it mean to be cholinergic and which receptors are cholinergic?

A

bind ACh

  • sympathetic and parasympathetic preganglionic neurons
  • parasympathetic postganglionic neurons
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7
Q

what happens to vesicular membrane once neurotransmitters are released into cleft?

A

it is recycled as well

  • moves up side of axon terminal, then endocytoses and becomes another synaptic vesicle
  • coated by clathrin
  • energy for recycling from dynamin
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8
Q

describe types of glutamate receptors

A
  • metabotropic
  • ionotropic
    • AMPA
    • NMDA
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9
Q

what is the difference b/w AMPA and NMDA glutamate receptors

A

AMPA

  • permeable to Na+, K+
  • needs only Glutamate

NMDA

  • permeable to Na+, K+, Ca2+
  • need Glutamate + partial membrane depolarization
  • important in learning and memory
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10
Q

what blocks the NMDA channel in the resting or hyperpolarized state?

A

Mg2+ is attracted to the negative charges on the inside of the cell membrane, but is not permeable -> clogs pore

partial depolarization makes the cell a little less negative, so Mg2+ isn’t attracted anymore -> Na+, K+, Ca2+ can enter

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11
Q

describe structure of glutamate ionotropic receptors

A
  • 5 subunits
  • TM2 segment forms hairpin loop w/i membrane
  • requires binding of two transmitter molecules to open
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12
Q

what happens to glutamate after it has bound receptors in the synaptic cleft and been released?

A

-taken up into glial cells -> converted into glutamine -> cycled back to nerve terminal for conversion to glutamate
(example of a non-neuronal cell critical for fxn of synapse)

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13
Q

describe GABA receptors

A
  • 5 subunits, each w/ 4 transmembrane segments
  • used by inhibitory neurons in brain
  • two types:
    • GABAa: ionotropic GABA gated Cl- channel
    • GABAb: metabotropic K+ channel
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14
Q

describe glycine receptors

A
  • 5 subunits, each w/ 4 transmembrane segments
  • less prominent than GABA receptors
  • used by inhibitory interneurons in spinal cord
  • ionotropic glycine gated Cl- channel
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15
Q

examples of metabotropic receptors

A
  • alpha and beta-adrenergic receptors: epi and norepi
  • GABAb receptors
  • metabotropic glutamate receptors
  • serotonin receptors
  • neuropeptide receptors
  • odorant receptors
  • certain taste receptors
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16
Q

describe how GPCRs are opened by direct interaction w/ the channel following G protein activation

A
  • transmitter binds -> receptor conformation change -> exposes binding site for G protein intracellularly
  • G protein associates w/ transmitter-receptor complex -> is activated for GTP-GDP exchange
  • GTP replaces GDP -> alpha subunit dissociates from G protein -> exposes active site which binds to channel
  • channel opened
17
Q

describe how GPCRs are opened by indirect interaction w/ the channel following G protein activation

A
  • transmitter binds -> receptor conformation change -> exposes binding site for G protein intracellularly
  • G protein associates w/ transmitter-receptor complex -> is activated for GTP-GDP exchange
  • GTP replaces GDP -> alpha subunit dissociates from G protein -> exposes active site which binds adenylyl cyclase
  • release of many molecules of cAMP
  • cAMP activates protein kinase -> phosphorylates channel
  • channel opened
18
Q

what are advantages of G protein mediated signaling over ionotropic signaling?

A
  • goes through second messengers -> multiple channels are activated -> amplification of signal
  • b/c channels are phosphorylated, they stay open longer -> longer lasting effects