Cellular Neuroscience (Structure Of Neurons)

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Plasma Membrane

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Allows for ion gradient

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Microbodies

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Mainly vesicles
Allows for transportation

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Electron Microscopy of a Neuron Cell Body

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- have characteristic structure (varies among types)
- shows makeup of a neuron

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Where Action Potential is Initiated

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Axon Hillock

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Where Synapses Occur

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- On synaptic spines (usury excitatory)
- On cell body (usually inhibitory)

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Neuronal Cell Body

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The same as in other cells

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Epithelial Blueprint of Neurons

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- Cell Membrane
- Cytoplasm

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Cytoplasm

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- Cytosol (includes cytoskeleton matrix)
- Membraneous Organelles

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Location of Lower Motor Neurons

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Found in Ventral Horn in the Spinal Cord

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Nucleus Functions

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- serves as transcriptional control center (contains cell's genome)
- contains the chromosomes necessary for the production of mRNA

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Nucleolus Functions

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Produces rRNA (ribosomal RNA)

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Genes Functions

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- encode mRNA (transcription)

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mRNA

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(Messenger RNA)

A duplicate complement of the information contained in the genes

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What Happens to mRNA after Transcription?

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mRNA leaves the nucleus and can be translated in the cytoplasm to produce proteins

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Translation

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(protein synthesis)

- DNA -> RNA -> proteins
- ribosomes read info in amino acids and use it to create proteins
- golgi directs proteins to destination

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(2) Subunits of Ribosomes

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1. Small subunit: binds to the mRNA
2. Large subunit: binds to the tRNA and amino acids

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How Ribosomes Translate

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- ribosomes bind to mRNA and use it as a template for the correct amino acid sequence of the protein:

1. the amino acids are attached to tRNA (transfer RNA) which enter the ribosome and bind to the mRNA
2. The ribosome moves along the mRNA "reading" it's sequence and producing a chain of amino acids

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Membrane Bound Ribosomes

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- membrane-bound to the rough ER
- synthesize proteins needed in some organelles or for exocytosis
- the newly produced polypeptide chains are inserted directly into the ER by the ribosome and are then transported to their destinations through the secretory pathway

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Free Ribosomes

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- can move about anywhere in the cytosol, but are excluded from the nucleus and other organelles
- the proteins they form are released into the cytosol and used within the cell

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Endoplasmic Reticulum

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- network of tubules, vesicles, and cisternae throughout cells
- Rough ER and Smooth ER

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Rough ER

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- synthesizes proteins
- is studded with ribosomes
- works with the golgi complex to target new proteins to their destinations

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Smooth ER

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- synthesizes lipids and steroids
- metabolizes carbohydrates and steroids
- regulates calcium concentrations

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Golgi Apparatus

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- factory in which proteins received from the ER are further processed and sorted for transport to their final destinations
- has a front receiving face (cis-end) and a backend (trans-face) from which molecules are discharged into secretory vesicles

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Most Common Alteration of Golgi Apparatus

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Addition of sugar chains to proteins and lipids which then collect in the cisternae and eventually bud off in a secretory vesicle

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Glycoprotein

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Adding sugar to a protein (Golgi Apparatus)

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Glycolipid

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Adding sugar to a lipid (Golgi Apparatus)

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Mitochondria

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- Cellular power plants

- necessary for all cell's surival

- cumulate in areas of cell which need excitability

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Mitochondria Functions

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- Primary Function: to generate energy in the form of ATP

- building, breakdown and recycling of proteins

- regulation of membrane potential and signal transduction

- cell signalling (eg. through reactive oxygen species production)

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ATP

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(adenosine triphosphate)

- produced by mitochondria in the "citric acid cycle" or "Krebs cycle"

- hydrolysis of these provides chemical energy for the cell

- necessary for all neuron functions

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How Mitochondria Regulate Membrane Potential and Signal Transduction

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via energy production and regulation of Ca (2+) -storage and release

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Calcium Stores

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The ER and mitochondria have higher Ca (2+) levels compared with the cytoplasm

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ER and Calcium Storage

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The ER has 2 pharmacologically different Ca (2+) stores, both of which are opened by physiological cellular events:

- PLC: activation of IP3 metabolism

- Ryanodine Store: elevation of cytosolic Ca (2+)

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Internal Calcium Regulates:

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- second messenger signaling

- the gating and kinetics of voltage-gates and ligand-gated channels

- gene expression

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Mitochondria and Calcium Storage

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mitochondria acts as a slow Ca (2+) buffer

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Cytoskeleton

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structural proteins of neurons

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Cytoskeleton Functions

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- provide a structural framework for the cell (serve as a scaffold that determines cell shape, organelle positions, and general organization of the cytoplasm)

- responsible for movement of cell

- responsible for internal cellular movements (transport of organelles, mitotic chromosomes, and vesicles)

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(3) Major Parts of the Cytoskeleton

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- Actin Filaments (microfilament)

- Intermediate Filaments "neurofilaments" in neurons)

- Microtubules

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Actin Filaments

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(microfilament)

- smallest of cytoskeletal fibers (5nm in diameter)

- consists of 2 protein chains twined together like strands of pearls (each pearl = an actin protein)

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Functions of Actin Filaments

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- necessary for plasticity (changes in actin structures on dendrites records information)

- responsible for cellular movements (eg. contraction)

- Responsible for "pinching" during cell division

- Responsible for formation of cellular extensions

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Intermediate Filaments

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("neurofilaments" in neurons)

- intermediate in size (8-10nm in diameter)

- very stable

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Functions of Intermediate Filaments

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- form Keratin in epithelial cells

- form stable structures such as hair and fingernails

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Microtubules

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- largest of skeletal fibers (~20nm in diamter)

- hollow tubes

- very unstable (halflife of ~10 min. in a nondividing cell to as short as 20 sec. in a dividing cell) unless stabilized by GTP

- polarized

- have +end and -end

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GTP

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(guanosine triphosphate)

stabilizes microtubules by inhibiting depolymerization

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Functions of Microtubules

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- allows neurons to set a specific direction of flow (from polarity)

- responsible for cell movement

- responsible for moving materials within the cell itself (serve as tracks for motor proteins to move along)

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+End of Microtubules

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("anterograde transport")

- transport away from nucleus

- Kinesin motor proteins

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-End of Microtubules

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("retrograde transport")

- transport towards nucleus

- Dynein motor proteins

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Motor Proteins

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proteins which move organelles around the cell on microtubule tracks (attached by their feet and move vesicles back and forth)

- Kinesins

- Dyneins

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Track A Receptor

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controls pain (mutations of which make people unable to feel pain)

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Cell Membranes

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- important for neurons (channels rely on membranes so as to contain neurotransmitters, hormones, receptors, and maintain charge)

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Components of Cell Membranes

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- Phospholipid molecules (phospholipid bilayer)

- Transmembrane Proteins

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Phospholipid Bilayer Functions

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- provides matrix for proteins

- provides permeability barrier which keeps ions, proteins, and other molecules where they are needed and prevents them from diffusing into areas where they shouldn't be (impermeable to most water-soluble molecules

- helps regulate salt concentrations and pH by using proteins called ion pumps

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What the Phospholipid Bilayer is Permeable to

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- Gases (eg. CO2 and O2)

- Hydrophobic molecules (eg. Benzene)

- Small polar molecules (eg. H20 and Ethanol)

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What the Phospholipid Bilayer is Impermeable to

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- Large polar molecules (eg. Glucose

- Charged molecules (eg. Amino Acids and Ions)

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(3) Transmembrane Proteins

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- Carriers

- Channels

- Receptors (Anchors)

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Carrier Transmembrane Protein Functions

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- transport molecules across membrane against gradient

- "escort" molecules through the membrane in a series of conformational changes

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Channel Transmembrane Proteins

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- transverse the membrane multiple times

- exterior portion consists of 1 or more nonpolar amino acid helices which water avoids (locking protein into membrane)

- the nonpolar regions move towards water, "shoving" the protein back into the membrane

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Channel Transmembrane Protein Functions

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(transverse membranes and create pores)

- Passively transport molecules across the membrane

- Create tunnels that act as a passage through the membrane

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(2) Ion Channels

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- Ionotropic Receptors (direct ligand-gated)

- Voltage-Gated

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Receptor (Anchor) Transmembrane Protein

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- anchored to phospholipids in the membrane

- free to move about on the surface of the membrane

- exterior portion binds to hormones/other molecules which induces changes on interior portion

- interior portion translates external information into internal action

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Receptor (Anchor) Transmembrane Protein Functions

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- transmit information into the cell

- signal molceules bind to cell-surface portion of the receptor protein which alters the portion of the receptor protein within the cell, inducing activity

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Why are Channels Important?

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Primary Erythromelagia (PE) or "Burning Man Syndrome"

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Primary Erythromelagia (PE)

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("burning man syndrome")

- rare autosomal-dominant painful condition with spontaneous burning pain of feet and hands

- pronounced erytherma or increased skin temperature

- hyperexcitability (active without stimulation)

- Great mystery as to why only in hands/feet

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Primary Erythromelagia (PE) Mutation

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- snip mutation (single nucleotide)

- In gene SCN9A: which codes a sodium channel alpha subunit (protein Nav1.7)

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Opposite of Primary Erythromelagia (PE)

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- Palestinian family have mutation causing opposite effect (insensitivity to pain)

- not exclusive to hands and feet

- became circus performers

- An SCN9A channelopathy causes congenital inability to experience pain

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How Primary Erythromelagia (PE) is Treated

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- used to be treated by dipping hands/feet in ice water

- now treated with epileptic medications (to reduce excitability of sodium channels)

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Sodium-Potassium Pump

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- transporter protein

- "active" transport of ions across the membrane (requires energy)

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How Sodium-Potassium Pump Works

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1. Interior of pump binds to intracellular Na(+)

2. ATP phosphorylates pump with bound Na(+)

3. This causes conformational change allowing Na(+) to leave

4. Extracelluar K(+) binds to exposed sites

5. This causes dephosphorylation of protein

6. This triggers return to original conformation and K(+) moves into the cell and cycle repeats

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How Signal is Transmitted From One Point to Another Within a Neuron

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by a transient change in the electric field and its associated voltage (potential)

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(Chemical) Synapses

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- mediates neuron-to-neuron communication

- active zone is very dense

- vesicles hold neurotransmitters

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Dendritic Spines

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(post-synaptic terminals)

- site of excitability transmission

- different types (shapes) transduce signal differently and over different distances (play different roles in synaptic transmission)

- important for plasticity

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Type of Dendritic Spine Best at Transmitting Over Greater Distances

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mushroom-shaped dendritic spines

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Chronic Neuropathic Pain on Dendritic Spines

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- causes a reorganization of dendritic spines

- depends on signalling pathway called "rac1"

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"Vehicle"

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- Solvent (solution) that a drug is found or administered in

- shows that a response seen is due to the treatment being tested, not the solution it is in

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"Sham surgery"

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treatment or procedure performed which is similar to the one under investigation, but lacks a key component

(an important scientific control)