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

Receptor Theory

Alberts et al., Molecular Biology of the Cell

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

Synaptic Transmission

(cont’d) which cause the channels to open allowing, e.g., Na+ to enter the postsynaptic cell).

The entry of Na+ would cause a graded depolarization (e.g., EPSP) of the postsynaptic membrane.This graded depolarization can trigger an action potential “downstream.”

Fig. 12.17