Channel-linked Receptors
• aka: ligand-gated channels• a receptor type seen in synaptic transmission• rapid response (ms)• limited response
– depolarization– hyperpolarization– stabilization of membrane potential
• inhibition of depolarization• inhibition of hyperpolarization
Fig. 15-15, Alberts et al., Molecular Biology of the Cell
Non Channel-linked Receptors
• “second messenger” systems– “first messenger” = extracellular chemical
signal– “second messenger” = intracellular signal
• slower responses than channel-linked receptors
> 100 ms
• amplification of signal• varied responses
– protein phosphorylation– opening or closing of a channel
First Messenger
Second Messenger(s)
Alberts et al., Molecular Biology of the Cell , 3rd ed.
Second Messenger Systems
Major Responses
protein phosphorylation(regulation of enzyme activity)
regulation of ion channelsregulation of ion channels
Fig. 1-44Ganong
Fig. 1-42Ganong
“Physiologic effects” can include changes in gene expression.
G-protein Systems• GTP required for function• ligand binds to receptor• activated receptor
activates G protein• activated G protein
activates (or inhibits) an enzyme [or a channel]
Figs. 15-5 and 15-28Alberts et al., Molecular Biology of the Cell
Two Examples of G-protein Systems
adenylate cyclasepathway
phospholipase C pathway
phospholipase Cadenylate cyclase
second messenger
IP3
Alberts et al., Molecular Biology of the Cell, 3rd ed.
(cyclic AMP)
adenylate cyclase pathway (see Fig. 17.22)
phospholipase C pathway (see Fig. 17.23)
phosphodiesterase
Adenylatecyclase
Fig. 1-44Ganong
Fig. 1-42Ganong
PIP2 = a specific phospholipidPLC = phospholipase CIP3 = inositol trisphosphateDAG = diacylglycerolPKC = protein kinase CCaBP = calcium-binding protein
Two Examples of G-protein Systems
(e.g., calmodulin)
Note: G-protein-linked receptors are serpentine receptors that are “7-pass” transmembrane proteins
Enzyme-linked Receptors
• The receptor is also an enzyme.– e.g., The receptors for insulin and various growth
factors have tyrosine kinase activity.
• The receptor directly activates an enzyme.– e.g., The receptors for growth hormone and
various cytokines activate a peripheral membrane protein that is a tyrosine kinase.
Fig. 15-15, Alberts et al., Molecular Biology of the Cell
G-protein Systems and Catalytic Receptor Pathways Overlap
Fig. 15-61Alberts et al., Molecular Biology of the Cell
The Number of Receptors on the Cell Surface is Regulated.
• up regulation # of chemical signals # of receptors
• e.g., denervation hypersensitivity
• down regulation # of chemical signals # of receptors
• e.g., drug tolerance
• Both up regulation and down regulation are typically negative feedback processes.
Fig. 17.25
Synaptic Transmission
(e.g., cholinergic synapse)
The action potential arrives at axon terminal (“synaptic knobs”).The “passive” depolarization of the end bulb causes voltage-gated Ca++ channels to open.
The increase in cytosolic Ca++ stimulates the exocytosis of synaptic vesicles.
Fig. 12.22
Fig. 4-4, Ganong
Synaptic cleft
Synaptic Transmission
The contents of the synaptic vesicle are chemical signals (neurotransmitter molecules) that diffuse across the synaptic cleft (a distance of 20-30 nm).The neurotransmitters reach the postsynaptic cell, where they bind to receptors, (e.g., channel-linked receptors,
Fig. 12.22
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