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Human Physiology

The study of functionality of living organisms at the cellular,

organ and systemic levels

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8/7/2019 Human Physiology I

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8/7/2019 Human Physiology I

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8/7/2019 Human Physiology I

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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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2

Neurotransmitter

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2

Myasthenia Gravis

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Nicotine Dependence