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Channel-linked Receptors aka: ligand-gated channels a receptor type seen in synaptic transmission rapid response (ms) limited response –depolarization.

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Presentation on theme: "Channel-linked Receptors aka: ligand-gated channels a receptor type seen in synaptic transmission rapid response (ms) limited response –depolarization."— Presentation transcript:

1 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

2 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

3 First Messenger Second Messenger(s) Alberts et al., Molecular Biology of the Cell, 3 rd ed. Second Messenger Systems

4 Major Responses protein phosphorylation (regulation of enzyme activity) regulation of ion channels Fig. 1-44 Ganong Fig. 1-42 Ganong “Physiologic effects” can include changes in gene expression.

5 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 15-28 Alberts et al., Molecular Biology of the Cell

6 Two Examples of G-protein Systems adenylate cyclase pathway phospholipase C pathway phospholipase C adenylate cyclase second messenger IP 3 Alberts et al., Molecular Biology of the Cell, 3 rd ed. (cyclic AMP)

7 adenylate cyclase pathway (see Fig. 17.22) phospholipase C pathway (see Fig. 17.23) phosphodiesterase Adenylate cyclase Fig. 1-44 Ganong Fig. 1-42 Ganong PIP 2 = a specific phospholipid PLC = phospholipase C IP 3 = inositol trisphosphate DAG = diacylglycerol PKC = protein kinase C CaBP = 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

8 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

9 G-protein Systems and Catalytic Receptor Pathways Overlap Fig. 15-61 Alberts et al., Molecular Biology of the Cell

10 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

11 Receptor Theory Alberts et al., Molecular Biology of the Cell

12 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

13 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

14 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


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