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Foundations 2 > 1-57 Signal Transduction in Nervous System > Flashcards

1-57 Signal Transduction in Nervous System Flashcards

1
Q

General scheme for autonomic nervous system signaling

A
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2
Q

Skeletal Muscle Ach signal release scheme

A
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3
Q

SNAP-25

A
  • Protein that tangles with vesicle snares and plasma membrane snares to make the snare bundle and hold vescile near the membrane
  • Calcium sensor binds the bundle to link vesicle release to intracellular calcium increase
  • SNAP-25 is target for botulinum toxin
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4
Q

Relevant toxins in nerve signal propagation

A
  • Tetrodotoxin:
    1. blocks Na+ channels on the presynaptic nerve terminal on the extracellular side to plug and prevent Na+ influx to propagate AP
    2. Also blocks Na+ influx on post-synaptic muscle cell
  • Mg+2 (etc.), other polyvalent cations
    1. Inhibit Ca+2 channels influx into cells
    2. Aminoglycoside antibiotics also inhibit Ca+2 influx
  • Botulinun toxin:
    1. Cleaves SNAP-25 part which prevents vesicle/membrane fusion and calcium sensing, so no vesicle release!
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5
Q

Nicotinic AcH Recpetor Blockers

A
  1. Curonium (rocuronium, vecuronium): non-depolarizing blockers to relax skeltal muscle during surgery, competitive inhibitor
  2. Succinylcholine: depolarizing blocker, depols cell before it blocks, used to relax skeletal muscle for intubation because super rapid and cholinesterase will degrade so you can administer an “overdose”
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6
Q

Myasthenic Gravis

A
  • Antibodies destroy postysynaptic nicotinic receptors
  • initial muscle strength may be normal BUT NMJ readily fatigues
  • many less Nicotinic receptors on post-synaptic muscle cell so unable to fire as often
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7
Q

Cholinesterase inhibitors

A
  • inhibit the degredation of ACh by cholinesterase
  • therefore, more Ach in the synaptic cleft for longer and can send stronger signals
  • NeoSTIGMINE: reversible cholinesterase inhibitor used to speed recovery from rocuronium/vecuronium after surgery
    • used to treat Myasthenia Gravis
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8
Q

Sarin

A
  • irreversible inhibitor, nerve gas
  • cholinesterase inhibitor, makes Nicotinic channels go haywire
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9
Q

General scheme for autonomic nervous system signaling

A
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10
Q

Adrenal medulla general signaling scheme

A
  • Epinephrine: can activate all catecholamine receptors (a1, a2, b1, b2)
    *
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11
Q

Sympathetic vs. Parasympathetic

A

Sympathetic:

  • pre-ganglionic origins: thoracolumbar
  • Synaptically: NE not degraded by cholinesterase (obviously) it is taken back up into nerve terminal (SLCs)
  • post-synaptic receptor: Norepepinephrine signals on to Alpha1 or Beta1 GPCRs (on smooth or cardiac muscle)

Parasympathetic:

  • pre-ganglionic origins: cranial-sacral
  • post-synaptic receptor: ACh signals on to muscarinic GPCR
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12
Q

Parasympathetic signaling in heart

A
  • ACh released by vagal stimulation slows the heart and slows cardiac conduction
    • Binds muscarinic ACh receptors of SA node
    • GPCR activated and beta-gamma subunit activated K+ channels
    • K+ goes out of cell and hyperpolarizes to reduce heart rate and cardiac conduction
  • Atropine: drug, competitive inhibitor at the Muscarinic receptors on SA node, will block parasympathetic input and keep heart rate high
    • used during spinal surgeries to be able to numb lower body but keep heart rate up
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13
Q

Atropine

A

Atropine: drug, competitive inhibitor at the Muscarinic receptors on SA node, will block parasympathetic input and keep heart rate high

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14
Q

Parasympathetic effect on airways?

A
  • Ach signals on to Muscarinic receptors in bronchioles
  • Activated GPCR->GTP-alphaQ activates PLC->activated IP3->Ca+2 release from ER->constricts
  • Drugs: atropine derivatives: iprATROPIUM, tioTROPIUM
    • ​competitive inhibitors of ACh at muscarinic receptors
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15
Q

-ATROPIUM, -TROPIUM

A

atropine derivatives: iprATROPIUM, tioTROPIUM

​competitive inhibitors of ACh at muscarinic receptors

used to treat asthma, COPD

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16
Q

Sympathtic signaling on smooth muscle vessels

A
  • NE released from sympathetic nerve endings onto alpha-1 receptors
  • GPCR of alpha1R->GTP-alphaQ activates PLC->IP3->Ca+2 release->constricts vessel
17
Q

Norepinephrine, phenylephrine mechanism in smooth muscle vessels

A
18
Q

Epinephrine effect on heart

A
19
Q

Increases in cAMP in cardiac vs. smooth muscle

A

Cardiac: increase cardiac contractility, Beta1 receptors

  • increase cAMP->increased L-type Ca+2 channel activity/Ca+2 entry->increased contratility and increased sarcoplastic reticulum Ca+2 stores

Smooth muscle: inhibit smooht muscle contration, Beta2 receptors

  • increased cAMP->reduces calcium entry and/or increases calcium removal->decreases contractility

Dependent on the activated PKA downstream phosphorylation targets

20
Q

Propranolol/Metoprolol

A

-OLOLs: competitive inhibitors of NE at beta-1 receptors in the heart

  • propranolol: inhibits b1 and b2
  • metoprolol: inhibits ONLY b1, so that b2 in lungs still working, use this drug in asthmatics
21
Q

Albuterol, salmeterol, formoterol

A

EROLs: beta2 agonists, relax smooth muscles in airways

22
Q

alpha2 receptors

A
  • activation causes membrane delimited gbeta/gamma sununits to activate or inhibit ion channels, follows the inhibitory motif (2 inhibits, 1 or 3 activates)
  • Clonidine: agonist of alpha2, to treat hypertension
  • NE and Epi are also agonists of alpha2 receptors
23
Q

Sympathetic tone

A
  • tonic vasoconstriction due to the tonic firing of SYMPATHETIC NERVES innerating vasculature
    • blood vessel are largely devoid of PARASYMPATHETIC innervation
  • Major determinant of BP: radius of blood vessels
24
Q

Blood pressure equations

A

Blood Pressure = Cardiac output x total peripheral resistance

Cardiac output = Heart rate x stroke volume

Total peripheral resistance = stuff / pi blood vessel radius^4

THEREFORE: changing radius of blood vessel is the most significant factor to effect BP

25
Q

Receptors on blood vessels? (2)

A
  1. alpha1: innervated from sympathetic nerve, fires NE, vasoconstrict
  2. beta2: no innervation but systemic EPI released from adrenal medulla, fires, vasodilate
26
Q

Summary of innervation and receptors of heart

A
27
Q

Summary of innervation and receptors of blood vessels

A
28
Q

Summary of innervation and receptors of lung bronchioles

A

Foundations 2 (27 decks)

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