Brain and Behavior Flashcards - Day 3
Immediate (primary) vesicles
1000 vesicles at the presynaptic membrane; Primary vesicles interact with the neuronal cell membrane in order to facilitate their release
Mobilization (secondary) storage vesicles
10,000 vesicles that can replace primary store in a few seconds
Reserve (tertiary) storage vesicles
100,000 vesicles in the axon
NMJ protein complex
the AChR is associated with several other proteins, including MuSK – often, defects in one of these other proteins can create a “bystander effect,” mimicking problems w/the AChR itself
Compound Muscle Action Potential
If lower motor neurons innervating a muscle are depolarized and there is normal NMJ transmission, then all muscle fibers will generate action potentials. The sum of these action potentials is called the CMAP.
Lambert Eaton Myasthenic Syndrome
Mechanism: auto-antibodies directed against presynaptic Ca2= channels results in decreased Ca2+ influx with depolarization and decreased release of ACh vesicles; Symptoms: fluctuating symmetric proximal limb weakness, worse in legs; may, but does not always, improve with exercise (more Ca2+ released w/repetitive depolarization)
Botulism: mechanism
Mechanism: botulinum toxins are proteinases that interfere with the fusion of vesicle & presynaptic membrane
Organophosphorous gases: mechanism
Irreversibly binds to AChE; repetitively activates the receptor b/c ACh remains unmetabolized in the synaptic cleft; raises the cell’s membrane potential – new resting potential is +45 mV; Na+ channels enter inactive state, causing paralysis of muscles (including diaphragm)
Myasthenia Gravis: mechanism
auto-antibodies directed against AChR (and, less commonly, MuSK); antibodies result in inflammation and destruction of motor end plate, reduced number of AChR; this results in a decreased EPP, which may not be greater than -50 mV, and an AP may not be generated
MG: symptoms
fluctuating skeletal muscle weakness and fatigue in the affected muscles; ptosis, double vision, chewing/swallowing, proximal limb weakness are common symptoms (15% pt have only ocular symptoms)
LEMS: symptoms
fluctuating symmetric proximal limb weakness, worse in legs; may, but does not always, improve with exercise (more Ca2+ released w/repetitive depolarization)
LEMS: epidemiology
1) young women predisposed to autoimmune dx – 30%, 2) pt with squamous cell lung cancer – 70% [neuro symptoms evident years before cancer is diagnosed]
Succinylcholine: MOA
activates AChR and maintains channel open for a longer duration; raises the membrane’s potential initially, causing contraction of muscle via opening of Na+ channels; however, Na+ channels enter an inactive state and paralysis follows
Pancuronium: MOA
Selective competitive antagonist to ACh for the receptor
Ionotropic messaging
ligand-gated ion channel receptors; fast; made up of multiple subunits (allows for diversity)
Metabotropic messaging
G protein-coupled receptors; slower; can modulate input; can activate a variety of post-synaptic events; more sustained
Inhibitory NTs
Glycine, GABA
Main inhibitory NT in the brain
GABA
Main excitatory NT in the CNS
Glutamate
Excitatory NTs
Glutamate, ACh, Serotonin, Histamine, Catecholamines (Epinephrine, NE, Dopamine)
Primary Glutamate receptor
NMDA; ionotropic; Permeable to Ca2+; Glycine co-agonist; Mg plug removed upon depolarization; currents slower & more sustained (long-term changes, minimal desensitization)
GABA A receptor
Ionotropic; Fast synaptic transmission in brain; post-synaptic, gates Cl-; made of α, β, γ subunits; problems: epilepsy, anxiety, addiction
GABA B receptor
Metabotropic; Slow, long-lasting inhibitory currents; pre- and post-synaptic; modulate K+ and Ca2+; drugs that work here include GHB, ecstasy
ACh receptor types
nicotonic (ionotropic), muscarinic (metabotropic)
