human physiology i
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Human Physiology
The study of functionality of living organisms at the cellular,
organ and systemic levels
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Central Nervous System
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Blood Brain Barrier
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Neurons
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An action potential is a sudden, transient depolarization of the membrane
followed by repolarization to the resting potential of about −60 mV
Action Potential
Rapid, transient, all-or-none electrical activity that is propagated in the plasmamembrane of excitable cells such as neurons and muscle cells. Action potentials, or
nerve impulses, allow long-distance signaling in the nervous system
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Synapses
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Neuronal Circuits
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Release of neurotransmitters and the recycling of
synaptic vesicles
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Synaptic-vesicle and plasma-membrane proteins important forvesicle docking and fusion
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Sequential activation of gated ion channels at aneuromuscular junction
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NeurotransmitterAcetylcholine
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Mechanisms for the formation of postsynaptic AChR aggregates
1. Redistribution - diffusion of AChRs in the plasma membrane
2. Local synthesis and insertion of new AChRs at the postsynapticsites
3. Reduction of extrajunctional AChRs – electrical activity reduces AChRnumber
All three mechanisms are involved!!
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1. AChRs are uniformly distributed at high density (100-1000/ µm2) in theembryonic myotube membrane.
2. Nerve contact triggers the formation of AChR clusters (10000/ µm2),
and disappearance of extrasynaptic AChRs (density < 10 / µm2)
1. Clustering of ACh receptors
AChR clustering labeled with a-bungarotoxin (α−Btx),
a cobra snake toxin that binds irreversibly with AChR
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2. Synthesis of AChR is regulated by neuregulin
Neuregulin/ARIA secreted by motor nerve terminal induces an increase inAChR gene transcription in the subsynaptic nuclei.
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3. Reduction of extrajunctional AChRs density depends on nerve/muscleactivity
• Cut nerve or block AChR function results in maintenance of high extrasynaptic
AChR density
• Stimulate the muscle reduces extrasynaptic AChR density
(ACh hypersensitivity)
(ACh hypersensitivity)
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Neurotransmitter
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Myasthenia Gravis
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Nicotine Dependence