BIO 325 CH 12 First Half: Neurons

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Whole animal integration

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1

Whole animal integration

Processing of sensory, endocrine, and CNS information to promote homeostasis

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2

Nervous vs Endocrine

Nervous responds rapidly but over a short period of time and more locally

Endocrine responds slowly but over a longer period of time

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Neuron

Functional unit Amitotic Receive and generate electricity and chemical signals

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4

In terms of ER or Ribosomes, the hillock and axon have

None

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5

Receptor vs Effector

Receptors are afferent in that they bring impulses towards the CNS

Effectors are efferent in tat they carry responses from the CNS into the body

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6

Classification of Neurons

multipolar, bipolar, unipolar

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7

Different types of transport mechanisms

Kinesisn: + end directed (toward nucleus), anterograde Dynein: - end directed (toward synapse), retrograde

Both are ATPases

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Anterograde vs Retrograde

Anterograde: Toward the axonal terminal where neurotransmitters, mitochondira, cytoskeletal elements and more

Retrograde: Towards the perikaryon, organelles being returned for degradation

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Unmyelinated vs Myelinated

In unmyelinated fibers, current flow is limited by resistance of the membrane, in myelinated fibers the current stays inside the fibers and less APs needed (propagation is better)

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10

Microglia Cells

main resident immunological cells of the CNS Function as WBCs (as they are derived from them)

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Astrocytes

Star shaped gial cells that make up the majority of the CNS

Regulate ionic conditions in the intracellular space, uptake and or breakdown of neurotransmitters interacts with blood vessels to form the blood brain barrier may regulate neurological function

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12

Oligodendrocyte

Mylein producing cells of the central nervous system

a single oligodendrocyte myelinates many axons (as opposed to schwann cells)

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13

Ependymal Cells

Cells which line the ventricles of the brain and central canal in the spinal cord

typically cuboidal and have cilia produce cerebrospinal fluid

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14

Choroid Plexus

Responsible for production CSF This plus the arachnoid membrane act together to form a barrier between CSF and blood

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15

Electronics

Resistance: Rate an object limits current flow

Capacitance: Ability to store charge. More C more ions a membrane can separate and store for a give difference

Current: Movement of charge Voltage: Electrical potential difference

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Decremental Spread

Axons have very low spread because the V is regenerated at each node or along an unmylenated axon

This refers to the drop in voltage the farther you get from the source since you are continuously passing through areas of lower resistance

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Resting Membrane Potential

The membrane potential is differecne in electrical charge between the inside and the outside of a neuron

Cl- higher on outside always, same with Ca2+. Ca2+ also found in vesicles - they are more for a regulation than a gradient

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Ion Pumps

Help maintain the concentration of major ions. Ions diffuse with respect to their own concentration gradients

K+ dictates the resting potential (since its easier for it to diffuse via leak channels)

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19

Electrogenic Pumps

Have a conformational change when an ion binds

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20

3 Important Things to Electrical Contributions of Ions to Membrane Potentials

Ion mobility, selective ion permeability, ion concentration gradient

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21

Ion Mobility

Velocity of the ion/potential gradient or field strength. Depends on?: Nature of the ion including frictional forces, concentration of the solution, temperature, applied potential gradient

Ions of smaller radius have lower mobility in the hydration layer

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Ionic Permeability

Na, Cl, and Ca2+ have low permeability, K+ is high

Selective Permeability through the lipid portion is due to: Molecular Weight Hydration Layer Charge

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Ion Concentration Gradient

In general, Na+ is low in the cell and K+ is high in the cell Squid axons are easy to use for readings

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Donnan Equilibrium

Gradient that develops when 2 solutions are sperated by a membrane permeable to only some ions in the membrane

Magnitude can be determined by the Nernst Equation:

Eion= 62mV(Log[ion]outside/[ion]inside)

Equation treats dilute ions as an idea gas

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25

Goldman Equation

Used to look at all of the ions for resting membrane potential

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Membrane potential changes in response to opening or closing of

Protein Channels

When K+ channels open, K+ diffuse out making the inside of the cell more negative -> hyperpolarization

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Hyperpolarization

An increase in magnitude of the membrane potential Triggered by K+ cells leaving the cell membrane

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Depolarization

An decrease in magnitude of the membrane potential Na+ diffuses into the cell

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Sodium Channels

Voltage Gated: There are 10 types and found in excitable tissues

Epithelia Sodium Channels: Found in places like the kidney where absorption takes place

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Transient Sodium Channel

Rapidly activating and inactivating

Inactivated by tetrodotoxin and saxitoxin

Rectified = resistance and conductance vary with voltage

Mediates rising phase - depolarization of action potential

3 conformations: closed, open, inactivated

beta-axillary subunits involved in channel localization and interaction with cell adhesion molecules, extracellular matrix and intracellular cytoskeleton

alpha- functional subunit- functional sodium channek

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31

Molecular Structure of Voltage Gated Sodium Channel

2 subunits with 4 domains (I-IV) with 6 membrane spanning segments 4 domains surround an aqueous channel pore

Segment 4 of each domain responds to voltage-it rotates and slides outward when depolarized

P loop connecting segment 5 and 6 lines pore and helps mediate ion selectivity

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32

Hodgekin Cycle

Inital depolarization of cell causes Na+ channels to open, which by opening cause more Na+ chanels to open which further depolarizes the membrane

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Calcium Channels

Dont have an inactivation state, are either open or closed

Ca2+ higher outside the cell or in vesciles or organelles

Is all 1 protein

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4 types of Ca2+ CurrentsIt

IT: Low Threshold

IL: High Threshold

IN: Rapidly Inactivating

IP: Purkinje Cells

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IT Channel

– Tiny current

– Transient, rapidly inactivating

– Threshold is negative to -65mV /low voltage activated

– Involved in cardiac pacemaker--produces the pacemaker potential in the SA node of the heart

– expressed in the heart, central and peripheral nervous systems, kidney, smooth muscle, reproductive organs and endocrine organs.

– Not sensitive to calcium blockers

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IL Channel

•Long lasting-large sustained conductance; slow inactivating

•Threshold about -20mV

•High voltage activated

• Ca+2 spikes of dendrites • synaptic transmitter release in skeletal muscle and synaptic transmitter release in skeletal muscle and brain brain

• plateau phase-slow inward current of action potential of cardiac muscle

•May trigger release of internal calcium

•Regulated by cAMP dependent protein kinase- phosphorylation enhances probability of channel opening

•Are sensitive to calcium blockers

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IN Channel

– 'N' for "Neural-Type“ – High voltage activated

– Threshold about -20mV

– Found primarily at presynaptic terminals and are involved in neurotransmitter release. Strong depolarization by an action potential causes these channels to open and allow influx of Ca2+, initiating vesicle fusion and release of stored neurotransmitter.

– Not sensitive to many calcium blockers

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38

IP Channel

– Activated by strong depolarization rapid inactivation-similar to IN

– Involved in transmitter release from Purkinje cells

– They are also found in Purkinje fibers in the electrical conduction system of the heart. Their properties are less well understood.

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Voltage Gated K+ Channels

Tetramer, each has 6 membrane spanning units

4 separate but identical proteins

Inner and outer faces have layers of Trp and Tyr that form a cuff around the pore, they pull the pore opening like a spring

Selectively allows gly tyr gly residues

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40

IK Channel

Rectified

Activated by strong depolarization

Delayed activation and slow inactivation

Mediates action potential repolarization

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41

IH Channel

Inward Rectifying Channel

Nonconducting at + potentials – Allows K+ to flow into rather than out of the cell

– Depolarizing current that is activated by hyperpolarization Ih

– Depends on interaction with phospatidylinositol 4,5 bisphosphate (PIP2)

– Contributes to cell excitability-rhythmic spiking and burst activity

– In vertebrate cardiac muscle, frog skeletal muscle and starfish eggs

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42

IC Channel

Calcium Activated

– Activated by increase in calcium concentration

– Mediates action potential repolarization and interspike interval

– Creates long hyperpolarized period

– Burst firing due to calcium influx

– Potassium moves out

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43

IK Channel

Potassium leak channels

contribute to the resting membrane potential

are constitutively open

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44

IA Channels

Fast transient/inactivating channel

• In sensory organs-in information encoding membranes

• Can encode a sustained depolarizing stimulus into a sustained rate of action potentials

• Delays onset of firing lengthens interspike interval

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45

Voltage Dependent Chlorie Channel

Involved in hyperpolarization and moderating neuronal exitability by determining the postsynaptic response to GABA and glycine

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46

Ligand Gate Chloride Channels

Modulatory dunction in postsynaptic response evoked by activation of ligand gated Cl- channels, such as GABAA receptors (GABBARs)

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