Excitability of cells Flashcards
what are the 3 general functions of neurons?
- collect signals
- integrate them
- transmit/output them to produce a response
what does the nervous system do?
- system of communication that allows can organism to react rapidly and modifiably to changes in the environment
- electrical signals provide rapid, reliable and flexible means for neurons to receive, integrate and transmit signals
- chemical messengers and receptors between and within cells provide more flexibility via inhibition
what are the 2 electrical properties of neurons?
Action potentials
- all or nothing (fixed size)
- travel in one direction
- can’t summate
- long distances
- coded by frequency
Graded potentials
- variable size
- can travel in both directions
- can summate
- local signals
- coded by amplitude/size
when is a neuron said to be at rest?
- when it is not generating either APs or GPs
- when the inside of the neuron is more negative than the outside
what is the voltage of the membrane at resting potential?
-65mV
how is potential difference measured?
- connect neuron to voltmeter
- microelectrode filled with KCl is inserted into the neuron
- another electrode made of silver chloride is inserted into fluid surrounding the neuron
- there is no potential difference in the extracellular solution (0mV)
- as soon as the microelectrode enters the resting cell, the voltage changes to between -65mV and -90mV
why do neurons have a resting potential?
- selectively permeable membrane
- unequal distribution of charged ions
- physical forces
how is the membrane selective and how does it maintain unequal charge?
- channels confer selectivity
- pumps assist unequal charge distribution e.g. sodium-potassium pump (3Na+ out, 2K+ in)
how is the membrane selective and how does it maintain unequal charge?
- channels confer selectivity
- pumps assist unequal charge distribution e.g. sodium-potassium pump (3Na+ out, 2K+ in)
which 2 forces control flow of ions across the neuronal membrane?
- Diffusion:
2. electrical fields
how does diffusion effect ion flow?
Diffusion:
- net movement from high conc to low conc
- lipid bilayer provides barrier to diffusion to form concentration gradient
- open ion channels provide route for ions to flow down conc gradient by passive diffusion
- diffusion continues until equilibrium is reached
how do electrical fields effect ion flow?
- opposite charges attract and like charges repel
- because ions are charged, they form an electric current (measured in Amperes)
- current flow depends on:
- electrical potential (voltage)
- electrical conductance (measured
in siemens) - electrical resistance (ohms)
if no channels are open, conductance is 0
what are the key ion pumps?
K+/Na+ ATPase:
- exchanges internal sodium for extracellular potassium against their conc gradients
- requires ATP
Ca2+ pumps:
- transports Ca2+ out of neurons to maintain low intracellular calcium
- important as calcium is a signalling ion
- changes in calcium conc is detected by proteins and used to control cell functions
- high intracellular calcium is toxic so would kill neurons
why are ion pumps essential?
- they set up ionic gradients across neurons
- they enable the existence of resting potential
what is the equilibrium potential (Eion)?
- the membrane potential that would be achieved if the membrane were selectively permeable to that ion
- established when the electrostatic force counteracts the diffusional force
what is the Nernst equation used to calculate?
- the equilibrium potential (Eion) of an ion
- RT = temperature
- z = charge of ion
- F = Faraday constant
- log(ion conc outside/ion conc inside)
how is the Nernst equation limited?
- it does not take into account the permeability of other ions
What is the equilibrium potential of a membrane at rest?
- neuronal membrane is permeable to K+ at rest
- therefore the membrane potential is close to Ek
what are the properties of K+ channels and how do they set up ionic gradients?
- have 4 subunits, each with 6 transmembrane domains
- because membrane is highly permeable to K+ at rest, changes in K+ conc can have massive effects
- increasing extracellular potassium causes a shift in Ek
- this causes Ek to become more positive, causing depolarisation
what is the Goldman equation used for?
- for calculating the real membrane potential by taking into account the permeability of other ions
how is information encoded in the nervous system?
- action potentials
- graded potentials
what are the characteristic features of an action potential?
- rising phase: stimulus causes rapid depolarisation of the membrane
- overshoot: membrane potential is above 0mV (around +40mV)
- falling phase: rapid repolarisation of membrane
- hyperpolarisation: membrane potential becomes too negative
- undershoot: sodium-potassium pump returns membrane potential to resting
how fast is AP generation and what is its max frequency?
- 2 milliseconds to be generated
- max frequency = 500Hz
how are APs generated?
- a stimulus (e.g. activation of stretch receptor, or an excitatory neurotransmitter) cause sodium voltage-gated ion channels to open
- influx of Na+ causes depolarisation of the neuron
- if sufficient depolarisartion allows membrane potential to reach threshold, an AP is trigered
- if the depolarising stimulus is prolonged, a train of APs will be generated
what are the properties of APs?
- transient, rapid and reversible change in membrane potential from - to +
- different types of excitable cell may have different types of AP
- all APs are the same size
- they travel in one direction
- they do not decrease in size as they travel down the axon
how does change in membrane permeability cause an AP?
- a neuron is depolarised when the permeability to Na+ is inccreased (Ena) - +62mV
- if a cell at rest is Ek (-80mV), the net driving force on Na+ will be -80 - 62 = -142mV
- large potential difference forms a large conc gradient which allows Na+ infux
- causes rapid depolarisation
- after 1ms, Na+ channels shut ad K+ current dominates, resulting in outward potassium
what is the structure of voltage-gated Na+ channels?
- 6 transmembrane domains
- 4 other domains
- one transmembrane domain has many positive charges due to it containing positive amino acids
- when membrane is depolarised, amino acids undergo conformational change and move to the outside
- this causes the opening of the pore so Na+ can move in
How do Na+ channels open in response to depolarisation?
- conc of charge near plasma membrane affects voltage sensors
- if the charge reaches threshold due to depolarisation, conformational change is caused to open the channel
How do Na+ channels become inactivated?
- occurs in 1ms - why APs are so brief
- membrane potential must repolarise so channels can be activated again
- absolute refractory period
what are delayed rectifying channels?
- these are potassium channels which open slowly with a delay of 1ms
- this is to rectify/restore the membrane potential
- relative refractory period occurs while voltage-gated channels are open
give examples of useful poisons involved in APs
- Tetraethylammonium, TEA. K+ channels
- Lidocaine Na+ channels
- Saxitoxins, STX. Dinoflagellates (sp.) Na+
- Tetrodotoxin, TTX. Puffer fish (sp.) (fugu). Na+ channels
how are APs conducted along an axon?
- spread of Na+ causes local depolarisation of neighbouring parts of the axon
- although Na+ spreads in both directions, the Na+ channels behind the conduction are inactivated - refractory period
- the channels ahead of the conduction are open, so AP travels down axon in one direction to the terminal
in what manner are APs propagated?
- in a non-decremental manner
- meaning axons can generate APs along their entire length
how fast is conduction velocity?
10m/s
what factors influence conduction velocity?
- diameter
- myelination
- permeability of membrane
how does diameter affect Cv?
- resistance to flow of current is inversely proportional to the cross-sectional area of the axon
- the larger the diameter, the faster the conduction
- axons involved in life-threatening information tend to be large in diameter
How does myelination affect Cv?
- myelin is made by wrapping glial cells around axon membrane
- prevent current loss along axon by increasing membrane resistance and space constant = increase Cv
- forms nodes of ranvier = saltatory conduction
how does permeability of membrane affect Cv?
- conduction is slower if the membrane is discontinuous (holes in it)
- it tkaes longer for sufficient Na+ to accumulate down the axon to reach threshold
- leaky
- amplitude of AP decreases as distance increases if the membrane is leaky
examples of different conduction velocites:
- smallest unmyelinated axons = 0.2-1.5um = 0.5-2m/s
- most myelinated axons = 1-20um = 5-120m/s
- squid giant axon (unmyelinated) = 100-um = 25m/s
which is easier: myelination or increasing diameter?
myelination
what is saltatory conduction?
- breaks in myelination form nodes of ranvier
- nodes of ranvier have high conc of Na+ channels there, allowing APs to jump from node to node
differences between axons and dendrites in conduction:
- dendrites have voltage-sensitive channels but don’t usually produce APs
- axons generate APs at axon hillock near the cell body
- sensory neurons lack as many dendrites, and their axon hillocks are located at sensory nerve endings
how are APs coded?
- frequency of APs is dependent on size of the stimulus
- the stronger the stimulus, the higher the frequency of APs
- enables encoding of stimulation intensity
what is the absolute refractory period?
- there is a limitation to the frequency of APs that can be generated
- no matter the strength of the stimulus, the neuron is incapable of generating another AP after one has just been produced
what is the absolute refractory period?
- there is a limitation to the frequency of APs that can be generated
- no matter the strength of the stimulus, the neuron is incapable of generating another AP after one has just been produced
what is the relative refractory period?
- when another AP can be fired, but requires a stronger stimulus due to the threshold being raised
what are graded potentials?
- not all-or-nothing
- can be excitatory or inhibitory
- caused by opening of neurotransmitter-gated ion channels
- opening/closing of K+ channels
- can summate
how can GPs summate?
- they integrate info from multiple inputs
- they add EPSPs and if it reaches threshold, causes AP
- neurons can have 200000 synapses = lots of integration
what is spatial summation of GPs?
- when multiple EPSPs arrive at several separated neurons, the AP produced overall is stronger
what is temporal summation of GPs?
- relies on high frequency of APs in a short time, close to each other on one axon, to cause large depolarisation
how can EPSPs be shunted?
- if the membrane is leaky, EPSPs become dissipated
- the shunting effect is caused by opening of selective cation channels which allow cations to leave the axon and decrease membrane potential
what are electrical synapses?
- pore between 2 neurons
- rapid - immediate depolarisation of adjacent axon
- can travel both ways
- examples: retinal neurons, glial junctions, cardiac muscle, smooth muscle
what are electrical synapses?
- pore between 2 neurons
- rapid - immediate depolarisation of adjacent axon
- can travel both ways
- examples: retinal neurons, glial junctions, cardiac muscle, smooth muscle