Nervous System Flashcards
What is Amyotrophic Lateral Sclerosis?
ALS is a motor neuron disease characterised by:
Progressive degeneration of upper (between brain and spinal chord) and lower (between spinal chord and muscle) motor neurons - disrupting signals required for movement of muscles,
Inability to initiate/control voluntary neurons so eventually can’t speak, eat, move and then breathe,
Doesn’t affect brain function so perfect cognition, sensory perception, thinking…
Exact cause unknown - equal genetic (20 genes associated so gene therapy not possible) and environmental
Genetic mutations cause dysfunction that leads to protein aggregation in upper/lower motor neurons (clogs cell leading to cell death), environmental factors are unknown.
Describe the disease progression of ALS.
Early symptoms are slight weakness in hands/limbs
In weeks-months - twitching/cramping of muscles, loss of motor control hands/legs, tripping/increased falling incidences, persistent fatigue, slurred speech
Late stage, beyond a year - difficulty breathing, difficulty swallowing, paralysis
2-5 years life expectancy after diagnosis
What is multiple sclerosis?
MS is a demyelinating autoimmune disease, affecting the conduction of electrical signals in CNS:
Myelin surrounds nerve and makes faster and more accurate so without myelin the information propagated can be affected so not propagated correctly
Develops/diagnosed in 20s/30s normally - wide range of symptoms including: blurred vision, uncontrolled voluntary movement, loss sensation/balance, life expectancy is reduced only slightly and symptoms managed
Pathophysiology includes:
Formation of lesions in CNS (plaques)
Inflammation due to autoimmune response
Destruction of myelin
Combined effects of disrupted signalling between neurons in CNS
Describe the symptom progression of MS.
Clinically isolated syndrome (CIS) - First episode causing inflammation and damages nerves (myelin)
Relapsing-Remitting MS (RRMS) - Follows predictable pattern of worsening then improving symptoms
Secondary-Progressive MS (SPMS) - If untreated, can progress into more aggressive/progressive form
Describe some specialised glial cells.
Astrocytes - most numerous cells in the brain, fill spaces between neurons and regulate chemical content of extracellular space
Schwann Cells - oligodendroglial cells that are specialised glial cells which myelinate axons
What is the Law of Dynamic Polarisation?
Information flows in one direction down neurons for cell-cell communication.
Dendrites collect electrical signals, they are integrated in the cell body which generates outgoing signal to axon, which passes electrical signal down to another cell dendrites or to an effector cell.
What are afferent axons?
Where are they found in the spine?
Sensory axons that take information from the periphery/skin to the CNS.
Found in the dorsal roots and the spinal cord.
What are efferent axons?
Where are they found in the spine?
Motor axons that take information from the CNS to muscles to inervate.
Found in the ventral roots and the spinal cord.
What are excitable cells?
Electrically charged cells using electrical currents to:
Sense stimuli (chemicals, pressure, pain, touch…),
Transmit information to each other (often over long distances),
Cause actions (contract muscle fibre, release messenger like hormone/neurotransmitter…).
How are electrical currents made in biology?
The movement of ions in a solution (since living things exist in water environment).
Mainly Na+, K+, Cl-, Ca2+
Phospholipid membranes are impermeable to ions.
What two ways can ions cross the phospholipid membrane?
Through ion pumps and ion channels.
Describe the concentration gradients of Na+/K+/Cl- across the membrane.
What is the net charge?
Na+ higher extracellularly
K+ high intracellularly
Cl- high extracellularly
Net + charge extracellular, - charge intracellular.
Describe the action of the sodium-potassium pump.
Uses ATP to maintain concentration gradient by taking 3 Na+ out, 2 K+ into cell.
What are ion channels?
Membrane proteins which make pores or gates that allow ions to move across the lipid membrane down their concentration gradient.
Ion channels can be:
Selective - for particular ions (e.g. Na+, K+)
Switched to be open or closed by conformational change.
What are leak potassium channels?
Leak Potassium channels are open at rest (when cell is not excited) and responsible for setting the resting membrane potential (Vm=-65mV).
Regulated by pH, oxygen tension, stretch.
K+ goes out down concentration gradient, in down electrochemical gradient (since net - charge inside).
Equilibrium potential for potassium is when in and outflow of K+ is equal
What is the Nernst equation?
Estimates the equilibrium membrane potential for K+ (and thus the resting membrane potential).
For K+, Ek = -84 mV, which is low (normally -65 mV).
Neurons are permeable to other ions in addition to K+, notably Cl- ions which depolarise it slightly.
How do excitable cells communicate?
Stimuli causes action potential to be generated if the membrane is depolarised beyond the threshold.
A train of action potentials allows sensing a perception of severity (how long/hard a poke is…).
Pushing harder/longer on skin causes a greater number of action potentials, close together.
Why are action potentials important?
Long range communication (CNS & PNS):
Fast efficient signalling
Frequency and pattern of action potentials encode information
Bidirectional Communication
Motor commands to muscles
Feedback sensory information (proprioception, muscle tone, pain)
What happens when action potential communication becomes disrupted?
Conditions like:
Multiple sclerosis
Charcot-Marie-Tooth disease
Alzheimer’s disease
Locked-in syndrome
ALS
Describe the phases of the action potential.
- Resting potential - maintained by Na-K-ATPase
- Rising phase - rapid depolarisation to apex
- Falling phase - rapid hypopolarisation to repolarise
- Undershoot
- Return to resting potential so a subsequent action potential can be made
All or nothing - if reach threshold then get full action potential.
What happens during the rising phase of an action potential?
Voltage-Gated Na+ channels open when depolarised to threshold (-40mV) by induced conformational change in protein.
Na+ move rapidly into cell producing rapid depolarisation (rising phase).
Physical pore block inactivates channel after about 1ms.
Re-opening can occur once membrane returns to rest (-65mV).
What happens during the falling phase of an action potential?
Voltage-Gated K+ Channels open once depolarisation occurs.
Slow to open, 1ms after depolarisation.
Allows K+ to filter out of cell producing rapid repolarisation (falling phase).
Delayed rectifier as delay in open and reset of membrane potential.
Channels close once membrane potential returns to rest (-65mV).
What is the refractory period during an action potential?
The time in which an excitable cell is unable to generate a subsequent action potential.
Different cells have different refractory periods as they have different rates of how many action potentials it can do within a time.
What are the two types of refractory periods?
Absolute refractory period - when all Na+ channels are already open so can’t open more to produce another action potential
Relative refractory period - when after hyper-polarisation, undershoot means harder to reach threshold so low probability of generating action potential
How are action potentials propagated down the axon?
Na+ channels opened as threshold met because of some depolarised current passively flowing down axon.
Depolarisation at the front of wave, repolarisation behind.
