BRS - initial flashcard bulk 1

what is a neurone?

• excitable non-dividing cells of the CNS and PNS

• transfer electrical signals

• heterogenous morphology

in terms of morphology what are the 4 types of neuronal cells:

• unipolar

• pseudo-unipolar

• bipolar

• multipolar

unipolar neurone features:

• one axon projection

• no dendritic projection

pseudo-unipolar features

• one axonal projection that divides into 2

• no dendritic projection

bipolar features:

• one axonal projection

• one dendritic projection

multipolar features:

• one axonal projections

• multiple dendritic features

recall the 3 types of multipolar neurones:

1. purkinje

2. pyramidal

3. Golgi

recall the 3 main structural components of a neurone:

1. cell body (perikaryon)

2. axon

3. dendrites

describe the difference in the function of a dendrite and an axon:

• an axon is used to transmit signals to other neurones

• a dendrite receives signals from other neurones

Recall the five types of cell in the CNS:

• Neuron

• Oligodendrocyte

• Astrocyte

• Microglia

• Ependyma

name 4 neuroglia:

• Oligodendrocyte

• Astrocyte

• Microglia

• Ependyma

describe the role of oligodendrocytes:

• they produce glia which produce myelin

• allow signals to move faster across nervous system - amplify signal

what is the most abundant type of cell in CNS?

• astrocyte

describe the role of microglia?

• they are immune cells

• neuronal macrophages

describe the role of ependymal cells:

• epithelial cells that line the cerebral ventricles (brain) and spinal cord

describe the role of an astrocyte:

• structural support

• mop up excess NT and waste

What is the difference between oligodendrocytes & Schwann cells?

• Oligodendrocytes → produce myelin CNS, myelinate number of axons

• Schwann cells → produce myelin in PNS, only myelinate single axonal segment

what are the 4 main physiological ions:

1. Na+

2. K+

3. Ca2+

4. Cl-

which ions have high extracellular concentrations:

• Na+

• Cl-

which ions have high intracellular concentrations:

• K+

define action potential:

• the change in membrane potential that occurs in a neurone when a signal is being transmitted

what value is RMP:

-70mV

What is the state of the VGSCs and VGKCs during RMP?

• closed

what causes membrane depolarisation?

• opening of VGSCs

• influx of Na+

• further depolarisation makes it -40mV

what causes membrane repolarisation?

• opening of VGKCs

• efflux of K+

• membrane repolarisation restores it to -70mV

how is RMP restored?

• by Na+K+ATPase as AP leaves there is an imbalance between Na and K

• so pumps 3Na+ out of cell and 2K+ in

resting configuration:

• Na+ enters vestibule and upon phosphorylation → 3Na+ ions transported through protein

active configuration:

• Na+ removed from cell, phosphate detaches from pump

• conformational change

• K+ enters vestibule

nodes of ranvier definition

The gaps between the myelin sheath on axons aren’t covered in myelin

what is saltatory conduction?

• AP jumps using nodes of ranvier instead of whole axon

what happens at the end of an axon?

• AP unable to jump across axon terminal → stops here

Describe the process of neurotransmission across a synapse. (7)

1. membrane depolarisation due to Na+ influx

2. membrane repolarisation due to K+ efflux

3. AP triggers VGCCs at pre-synaptic terminal to open

4. Ca2+ influx causes vesicles exocytosis

5. NT binds to receptors on post-synaptic neurone

6. Influx of Na+ causes AP in post-synaptic neurone

7. NT dissociates from receptor and recycled in synaptic cleft (metabolised by enzymes/recycled by transporter proteins)

What happens to neurotransmitters after an action potential has been triggered?

• disassociate from receptor and metabolised by enzymes in synaptic cleft

• can also be recycled by transporter proteins

Recall the three types of communication that axons use to communicate with other neurones.

• Axodendritic synapse (axon-to-dendrite)

• Axosomatic synapse (axon-to-somatic cell)

• Axoaxonic synapse (axon-to-axon)

Order them in speed from fastest to slowest.

• Axoaxonic

• Axosomatic

• Axodendritic

What is a neuromuscular junction?

• neurones to muscle

Which neurotransmitter works at the neuromuscular junction?

Acetylcholine

What type of signalling is involved between the nerve and effecter cell?

paracrine NT release, only uni-directional

Which NT is involved in NMJs?

ACh

which post-synaptic receptor is involved in the NMJ?

nicotinic ACh receptors (nAChR)

Describe how the transmission of signal from a neurone causes muscle cells to contract.

• ACh binds to nAChR

• stimulates the influx of Na+ causing depolarisation into muscle cell and sarcoplasm

• depolarisation causes Ca2+ in muscle cell to be released from sarcoplasmic reticulum

• Ca2+ binds to myofibrils causing muscle contraction

What is an end plate potential?

local depolarisation of muscle fibres as a result of NTs binding to post-synaptic membranes

• graded potential depends on size of stimulus

What are miniature EPP?

smaller release of ACh

How is excitation of the post-synaptic neurone coupled to muscle contraction (excitation-contraction coupling)?

• ACh binds to nAChR activating it in skeletal muscle membrane (sarcolemma)

• stimulates the influx of Na+ causing depolarisation of sarcolemma produces AP

• AP travels through T-tubules

• depolarisation from sarcolemma activates dihydropyridine receptors (DHPR) causing conformational change

• this change is transmitted from RyR on sarcoplasmic reticulum → open and release Ca2+ from intracellular stores

• Ca2+ activates myofibril so muscle contraction occurs

3 disorders of NMJ:

• botulism

• MG

• LEMS

botulism features:

• inhibits release of ACh from pre-synaptic receptors

• muscle paralysis as can’t depolarise or contract

MG features:

• autoimmune disorder where antibodies block nAChR

• causes fatiguable weakness with repetitive use as muscles can’t contract or relax

LEMS

• autoimmune disorder where antibodies block VGCCs

• calcium can’t enter presynaptic neurone - no ACh release

How can myasthenia gravis (MG) be distinguished from LEMS?

In MG, there tends to be facial muscle weakness which is not typically characteristic of LEMS.

what is flux in the context of diffusion?

The number of molecules that cross a unit area per unit of time.

membrane potential definition:

difference in voltage between the inside and outside of the cell

voltage definition

difference in charges between two areas to create a gradient

current definition

current describes the movement of these ions across a concentration gradient

typical membrane potential of a resting cell:

• -70mV

• means inside of cell is slightly more negative than outside

When does movement of molecules across a membrane stop?

• when an equilibrium has been achieved

What is an electrochemical equilibrium?

• The state at which the concentration gradient of certain particles in and out of an environment has been opposed and balanced out by an electrical one

• no net movement of molecules

equilibrium potential definition

• membrane potential at which electrochemical equilibrium has been reached

• potential prevents further movement of molecules across cell membrane

What factors affect the opening and closing of ion channels? (3)

1. transmembrane voltage (membrane potential) e.g. VGCs

2. presence of activating ligand (attaching to them)

3. mechanical forces

What is the Nernst equation used for?

• to calculate the equilibrium potential of a cell using the concentrations of ions on either side of the membrane

• relies on assumption that membrane is permeable to ion in question

What is the Goldman-Hodgkin-Katz (GHK) equation used for?

• more accurate model of Nernst equation

• cell membrane has varying permeability to ions at different times

What are the typical intracellular and extracellular conc. of Na+ and K+?

• Na+ 150mM extracellular, 10mM intracellular

  • Eq usually +72mV

• K+ 5mM extracellular, 150 mM intracellular

  • Eq usually -90mV

What is depolarisation?

membrane potential becomes more positive → 0mV

What is repolarisation?

membrane potential becomes more negative (towards RMP)

What is overshoot?

membrane potential increases above 0mV

What is hyperpolarisation?

membrane potential decreases below RMP

what are graded potentials?

• change in membrane potential dependent on strength of stimulus

• many small stimulus, so to produce AP must reach threshold

What happens to graded potentials over time?

they decrease with distance

why do graded potentials decrease over distance

1. charge leaks out ion channels in membrane

2. cytoplasm and membrane offer resistance so signal weakens

What happens if the graded potential reaches a threshold?

triggers action potential

What is the difference between an action potential and a graded potential?

• graded potentials → variable in size, can summate decay with distance

• action potentials → fixed size, no decay, all-or-nothing events

Where does an AP occur?

in excitable cells

state 3 examples of excitable cells:

• neurones

• muscles cells

• some endocrine tissue

What is the purpose of APs? (3)

• transmission of information reliably and quickly over long distances

• cell-cell communication

• activates intracellular processes

what does permeability depend on?

conformational state of ion channels

What is the conformational state of ion channels at depolarisation?

VGSCs open

What is the conformational state of ion channels at sustained depolarisation?

VGSCs inactivated, VGKCs open

What is the conformational state of ion channels at hyperpolarisation/ repolarisation?

VGSCs closed, VGKCs open

Name the 5 phases of the AP

1. RMP

2. depolarisation

3. upstroke (after -55mV threshold is reached)

4. repolarisation

5. hyperpolarisation

describe the relation between permeability and RMP stage

• membrane more permeable to potassium than sodium ions due to leak channels

• Na+/K+/ATPase maintains gradients

• -70mV

• membrane potential closer to equilibrium of potassium (-90mV) than sodium (+72mV)

describe the relation between permeability and depolarisation stage

• membrane becomes more permeable to sodium than potassium as VGSCs open

• causes sodium influx

• depolarisation occurs

describe the relationship between permeability and the upstroke phase:

• reaches threshold of -55mV

• PNa increases bc VGSCs open quickly→ Na+ influx

• PK increases bc VGKCs open slowly → K+ efflux

• less K+ efflux than Na+ influx

• membrane potential → Na+ eqm potential (+72mV)

describe the relationship between permeability and repolarisation phase:

• PNa decreases due to sustained depolarisation

• VGSCs inactivated so no further influx of Na+

• PK increases as more VGKCs open and remain open so K+ efflux

• membrane potential → K+ eqm potential

Describe the hyperpolarisation phase.

• VGKCs are initially open so K+ leaves the cell

• membrane potential moves closer to K+ eqm

• VGKCs then close

• membrane potential returns to RMP

What is the purpose of the refractory period?

prevents neurone being re-stimulated immediately to allow for unidirectionality and limiting frequency

state 2 types of refractory period:

1. absolute

2. relative

describe the absolute refractory period :

• all VGSCs inactivated

• no AP triggered regardless of stimulus strength

describe the relative refractory period:

• some VGSCs have returned to resting state

• many VGKCs open and membrane hyperpolarised

• AP only triggered if stronger-than-normal stimulus reaches threshold

what happens during the absolute refractory period:

• Na activation gate is open

• Na inactivation gate is closed (Na can’t come in)

• eventually both gates become closed as this period continues (activation becomes closed due to repolarisation)

• no new AP can be triggered even with very strong stimulus

what happens during the relative refractory period:

• Na+ channels have recovered

• inactivation gate becomes open

• AP may be triggered if stimulus is stronger than normal

Describe two factors that affect the conduction velocity/propagation distance of an AP.

1. axon diameter: larger diameter → increase in AP velocity as less resistance and depolarisation spreads quicker

2. myelination: increased myelination → increase in AP velocity

Example of a common neurological condition that results from reduced myelination.

Multiple Sclerosis - degeneration of myelin sheath, nerve starts to lose its myelin = Slower nerve impulses → saltatory conduction not as effective

How are APs propagated across an axon by saltatory conduction?

1. threshold reached so VGSCs open

2. depolarisation

3. AP moves further along axon

4. Na+ sense the decay (resets)

5. AP activated in another region of the axon

What does saltatory conduction ensure?

1. Prevents AP spread

2. Increases resistance

3. Decreases capacitance

What is pharmacology?

the study of a chemical substance that interacts with a specific target within a biological system to produce a physiological effect

What are the three questions that we can ask to assess how drugs have an effect on hosts?

• Where is the effect produced?

• What is the target for the drug?

• What is the response produced after interaction with this target?

where is the brain is the effect of heroin produced?

1. peri-aqueductal grey region (analgesia)

2. ventral segmental area (euphoria)

3. solitary nucleus (cough suppression)

What are the responses to heroin?

• euphoria

• analgesia (painkiller)

• cough suppression

What is the target (receptors) for heroin?

Opioid receptors in the brain (exists naturally to interact with endorphins)

What is the main goal of pharmacology companies when producing drugs?

To produce a drug that looks very similar to an endogenous compound, but has stronger effects.

What are the four main drug target classes?

• Receptors

• Enzymes

• Transport proteins

• Ion channels.