Whole animal integration
Processing of sensory, endocrine, and CNS information to promote homeostasis
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
Neuron
Functional unit Amitotic Receive and generate electricity and chemical signals
In terms of ER or Ribosomes, the hillock and axon have
None
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
Classification of Neurons
multipolar, bipolar, unipolar
Different types of transport mechanisms
Kinesisn: + end directed (toward nucleus), anterograde Dynein: - end directed (toward synapse), retrograde
Both are ATPases
Anterograde vs Retrograde
Anterograde: Toward the axonal terminal where neurotransmitters, mitochondira, cytoskeletal elements and more
Retrograde: Towards the perikaryon, organelles being returned for degradation
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)
Microglia Cells
main resident immunological cells of the CNS Function as WBCs (as they are derived from them)
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
Oligodendrocyte
Mylein producing cells of the central nervous system
a single oligodendrocyte myelinates many axons (as opposed to schwann cells)
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
Choroid Plexus
Responsible for production CSF This plus the arachnoid membrane act together to form a barrier between CSF and blood
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
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
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
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)
Electrogenic Pumps
Have a conformational change when an ion binds
3 Important Things to Electrical Contributions of Ions to Membrane Potentials
Ion mobility, selective ion permeability, ion concentration gradient
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
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
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
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
Goldman Equation
Used to look at all of the ions for resting membrane potential
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
Hyperpolarization
An increase in magnitude of the membrane potential Triggered by K+ cells leaving the cell membrane
Depolarization
An decrease in magnitude of the membrane potential Na+ diffuses into the cell
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
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
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
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
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
4 types of Ca2+ CurrentsIt
IT: Low Threshold
IL: High Threshold
IN: Rapidly Inactivating
IP: Purkinje Cells
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
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
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
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.
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
IK Channel
Rectified
Activated by strong depolarization
Delayed activation and slow inactivation
Mediates action potential repolarization
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
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
IK Channel
Potassium leak channels
contribute to the resting membrane potential
are constitutively open
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
Voltage Dependent Chlorie Channel
Involved in hyperpolarization and moderating neuronal exitability by determining the postsynaptic response to GABA and glycine
Ligand Gate Chloride Channels
Modulatory dunction in postsynaptic response evoked by activation of ligand gated Cl- channels, such as GABAA receptors (GABBARs)