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Medcelična signalizacija -

- prenos živčnega signala

Lodish, H. et al.: Nerve cells. In: Molecular cell biology, W.H. Freeman & Co., New York.

Alberts, B. et al.: Membrane transport of small molecules and the electrical properties of membranes. In: Molecular Biology of the Cell, Garland Science, New York.

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Structure of typical mammalian neurons

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Hippocampalinterneurons

green - MAP2

red - synaptotagmin

Neurons communicate with many other cells

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A synapse

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Reception, conduction and transmissionof electric signals

Ion channels in neuronal plasma membrane:

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Origin of the resting PM potentialin a typical vertebrate neuron

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Electric potential across the cell PM

Nernst equation:

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Effect of changes in ion permeabilityon PM potential

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Passive spread of a depolarization of a neuronal PMwith only resting K+ ion channels

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Voltage-gated ion channels generate action potentials(cycles of membrane depolarization,

hyperpolarization, and return to the resting potential)

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Ion permeabilities during an action potential

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Structure and function of the voltage-gated Na+ channel

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Unidirectional conductionof an action potential

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Myelination of axons

50-100 membrane layers

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Formation and structure of a myelin sheath

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Myelination increases thevelocity of signal conductionfrom ~1 m/s to 10-100 m/s.

12 µm myelinated vertebrate axon600 µm unmyelinated squid axon

12 m/s

Radical reduction of neuronal volume

Evolution of vertebrate brain

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Signal transmission at a chemical synapse(frog neuro-muscular junction)

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A chemical synapse - schematically

~20 nm

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Neurotransmitters

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Synaptic vesicle cycle

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Excitatory and inhibitory responses in postsynaptic cells

Frog skeletal muscle- nicotinic AChR(ligand-gated ion channel)

Frog heart muscle- muscarinic AChR(G protein-coupled R)

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Activation of ligand-gated ion channels at a NM junction

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Nicotinic ACh receptor

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Fast synapses

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Muscarinic ACh receptor (M2)in the heart muscle PM

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Slow synapses

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An electric synapse - schematically

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Ukrivljanje membran

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McMahon & Gallop (2005) Nature 438, 590-596.

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Mechanisms of membrane deformation

McMahon & Gallop (2005) Nature 438, 590-596.

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Phospholipids have different shapes andlipid shape affects membrane curvature

Inverted-cone Cone

Sprong et al. (2001) Nat. Rev. Molec. Cell. Biol. 2, 504-513.

PSMS

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Lipid shapingPalmitoyl CoA

CtBP/BARS

Scales & Scheller (1999) Nature 401, 123-124.

- Enzymes that change lipid headgroup size- Flippases

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Mechanisms of membrane deformation

McMahon & Gallop (2005) Nature 438, 590-596.

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Amphipatic helix and membrane curvature

McMahon & Gallop (2005) Nature 438, 590-596.

BAR domains

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Role of LPAAT-mediated conversion of LPA to PAin one of the steps of synaptic vesicle formation (fission)

Schmidt et al. (1999) Nature 401, 133-141.

LPAAT

LPAAT

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Recommended reading:Chen, Y.A. and Scheller, R.H. (2001): SNARE-mediated membrane fusion.

Nat. Rev. Mol. Cell Biol. 2, 98-106 Gallop, J.L. et al. (2005): Endophilin and CtBP/BARS are not acyl transferases in endocytosis

or Golgi fission. Nature 438, 675-678. Huttner, W.B. and Zimmerberg, J. (2001): Implications of lipid microdomains for

membrane curvature, budding and fission. Curr. Opin. Cell Biol. 13, 478-484Huttner, W.B. and Schmidt, A.A. (2002): Membrane curvature: a case of endofeelin`…

Trends Cell Biol. 12, 155-158Ikonen, E. (2001): Roles of lipid rafts in membrane transport. Curr. Opin.

Cell Biol. 13, 470-477McMahon, H.T. and Gallop, J.L. (2005): Membrane curvature and mechanisms of dynamic

cell membrane remodelling. Nature 438, 590-596Peters, C. et al. (2001): Trans-complex formation by proteolipid channels in the terminal

phase of membrane fusion. Nature 409, 581-588Ringstad, N. et al (1999): Endophilin/SH3p4 is required for the transition from early to

late stages in clathrin-mediated synaptic vesicle endocytosis. Neuron, 24, 143-154Scales, S.J. and Scheller, R.H. (1999): Lipid membranes shape up.

Nature 401 ,123-124Schmidt, A. et al. (1999): Endophilin I mediates synaptic vesicle formation by transfer of

arachidonate to lysophosphatidic acid. Nature 401, 133-141Weigert, R. et al. (1999): CtBP/BARS induces fission of Golgi membranes by acylating

lysophosphatidic acid. Nature 402, 429-433