Membrane Potential and Action Potentials Flashcards
What is flux?
The number of molecules that cross a unit area per unit
of time (number of particles). i.e. molecules.m−2.s−1
Why is diffusion useful?
Useful for transport over short distances
Spontaneous
No energy input required
What are the properties of ions? (3)
Charged molecules
Opposite charges attract
Like charges repel
What is voltage?
Voltage = Potential difference
Unit: Volts
Generated by ions to produce a charge gradient (i.e. like a chemical battery)
What is current?
Current
Unit: Amps
Movement of ions due to a potential difference
What is resistance?
Resistance
Unit: Ohms
Barrier that prevents the movement of ions
How do you calculate voltage?
V= I R
current x resistance
How do you measure membrane potential?
To measure membrane potential a reference electrode is placed outside the cell. This is the zero-volt level.
Another electrode is placed inside the cell. It measures a voltage that is negative compared with the outside (i.e. reference).
All cells have a membrane potential. The difference in voltage between the inside and outside.
What is the cell membrane?
Lipid (hydrophobic) cell membrane is a barrier to ion movement and separates ionic environments.
The cell membrane can selectively change its permeability to specific ions.
What are ion channels?
Permeable pores in the membrane (ion channels) open and close depending on transmembrane voltage, presence of activating ligands or mechanical forces.
Ion channels can be selective for different types of ion (K+, Na+, Cl-, Ca2+).
When does movement across a membrane occur and when does it stop?
Movement across the membrane will occur when the concentration of the ion is different on one side of the membrane and will stop when equilibrium is reached.
Can some ions be pulled back through ion channels while diffusing to an area of lower concentration?
Yes
What is electrochemical equilibrium?
electrical forces balance diffusional forces
A stable transmembrane potential is achieved
What is equilibrium potential?
The potential at which electrochemical equilibrium has been reached. It is the potential that prevents diffusion of the ion down its concentration gradient.
How do you calculate equilibrium potential (E)?
The Nernst equation
How can the Nernst equation be simplified?
Na+ and K+ are the most important ions at determining what?
The resting potential of neurones
What is the extra and intra cellular concentration of Na+?
150mM extra
10mM intra
What is the extra and intra cellular concentration of K+?
5mM extra
150mM intra
What are the concentrations of other ions?
What are Ek and Ena?
EK and ENa are theoretical values. In reality biological membranes are not uniquely selective for an ion. Membranes have mixed and variable permeability to all ions (but, for neurones at rest K+»_space; Na+).
A typical resting membrane potential (Em) is -70 mV and not - 90 mV which is EK.
Each ion’s contribution to membrane potential is proportional to how permeable the membrane is to the ion at any time.
What is the GHK equation?
Goldman-Hodgkin-Katz
The GHK equation describes the membrane potential (Em) more accurately; P is permeability or channel open probability (0 = 100% closed, 1 = 100% open, 0.5 = open 50% of time), Subscript on P indicates the ion, [K+], [Na+] and [Cl-] represent concentration and the subscript i or o indicates inside or outside the cell.
What influences an ion’s diffusion?
It’s charge
What does the GHK equation allow?
Membrane potentials being estimated in more complex systems (many ions and variable permeability)
What is the resting membrane potential almost entirely due?
the movement of K+ ions out of the cell
What does depolarisation mean?
Membrane potential becomes more positive towards zero mV
What is repolarisation?
Membrane potential decreases towards resting potential
What does overshoot mean?
Membrane potential becomes positive
What is hyperpolarization?
Membrane potential decreases beyond resting potential
Why does membrane potential change?
Response to external stimulation or neurotransmitters
What are graded potentials?
Change in membrane potential is graded in response to the type or strength of stimulation
Graded potentials produce the initial change in membrane potential that determines what happens next – they initiate or prevent action potentials
What is the mechanism for decremental spread of graded potentials?
Charge leaks from axon and the size of the potential change decreases along the axon
When do AP occur?
Action potentials (AP) occur when a graded potential reaches a threshold for the activation (opening) of many Na+ channels resulting in an “all-or-nothing” event
Where do AP occur?
They occur in excitable cells (mainly neurons and muscle cells but also in some endocrine tissues)
What are AP known as in neurones?
In neurons they are also known as nerve impulses and allow the transmission of information reliably and quickly over long distances
What is the role of AP?
Play a central role in cell-to-cell communication and can be used to activate intracellular processes
e.g. in muscle cells, an AP is the first of a series of events leading to contraction
e.g. in beta cells of the pancreas an AP stimulates insulin release
What is the ionic basis of AP?
Permeability depends on conformational state of ion channels
- Opened by membrane depolarisation
- Inactivated by sustained depolarisation
- Closed by membrane hyperpolarization/repolarisation
When membrane permeability of an ion increases it crosses the membrane down its electrochemical gradient
Movement changes the membrane potential towards the equilibrium potential for that ion
Changes in membrane potential during the action potential are not due to ion pumps
What are the five phases of the action potential?
- resting membrane potential
- depolarising stimulus
- upstroke (extremely rapid)
- repolarisation
- after-hyperpolarization
What happens during resting membrane potential?
- Permeability for PK > PNa
Membrane potential nearer equilibrium potential for K+ (-90mV) than that for Na+ (+72mV)
What happens during depolarising stimulus?
- The stimulus depolarises the membrane potential
Moves it in the positive direction towards threshold
What happens during the upstroke
3.
Starts at threshold potential
Increase PNa because voltage-gated Na+ channels open quickly [Na+ enters the cell down electrochemical gradient]
Increase PK as the voltage-gated K+ channels start to open slowly [K+ leaves the cell down electrochemical gradient] Less than Na+ entering
Membrane potential moves toward the Na+ equilibrium potential
What happens during repolarisation?
Decrease PNa because the voltage-gated Na+ channels inactivate (block movement through channel) - Na+ entry stops
Increase PK as more voltage-gated K+ channels open & remain open
K+ leaves the cell down its electrochemical gradient
Membrane potential moves toward the K+ equilibrium potential
What happens at the start of repolarisation?
Absolute refractory period
Na channel activation gate is open Inactivation gate is closed
New action potential cannot be triggered even with very strong stimulus
What happens in the later stages of repolarisation?
Absolute refractory period continues
Activation AND Inactivation gates closed
What happens during after-hyperpolarization?
At rest voltage-gated K+ channels are still open
K+ continues to leave the cell down the electrochemical gradient
Membrane potential moves closer to the K+ equilibrium - some voltage-gated K+ channels then close Membrane potential returns to the resting potential
What also happens during after-hyperpolarisation?
Relative refractory period
-Some Na+ channels have recovered from inactivation – gate is open
- Stronger than normal stimulus required to trigger an action potential
Describe the time-course of changes in permeability?
What is the regenerative relationship between Pna and Em?
Once threshold potential is reached an AP is triggered
APs are “all-or-nothing” events. Once triggered a full-sized action potential occurs – positive feedback
Following an AP there is a refractory state where the membrane is unresponsive to threshold depolarisation until the voltage-gated Na+ channels recover from inactivation
Describe the ion movement during the action potential.
During AP Na+ enters the cell and K+ leaves the cell - only a very small number of ions cross the membrane to change the membrane potential - the concentration change is extremely small (<0.01%)
Ion pumps are NOT directly involved in the ion movements during the AP
The ion concentration gradients are restored following the action potential by K+ and Na+ ions being carried across the membrane against their concentration gradients by different types of ion transporter e.g. Na+/K+ ATPase
Membrane potential changes are…
graded or all-or-none
What is the all or none principle?
when a stimulus exceeds the threshold potential, the nerve will produce a complete response; otherwise, the response is graded and decays
What ion is responsible for repolarisation of the membrane?
K+
What opens the Na+ channels and what inactivates them during an AP?
Na+ channels opened by membrane depolarisation and inactivated by sustained depolarisation
What is passive propagation?
Small sub-threshold depolarisations decay along length of axon
Resting membrane potential re-established by more K+ channels opening
What alters propagation distance and velocity?
Internal (or axial) & membrane resistance and diameter of axon
Describe active propagation of the action potential.
It then moves forward, and the old negative bit is positive
and the positive part in front of the old negative becomes negative
The old active region returning to resting potential
Where are voltage gated channels mostly located?
at nodes (of ranvier)
How does action potentials link with nodes of ranvier?
What influences conduction velocity?
axon diameter and myelination
How fast do AP travel in small and large axons?
1 m/s in small diameter, non-myelinated axons
120 m/s in large diameter, myelinated axons
When does conduction velocity decrease?
Decreases with reduced axon diameter (i.e. re- growth after injury), reduced myelination (e.g. multiple sclerosis and diphtheria), cold, anoxia, compression and drugs (some anaesthetics)
Where do AP occur?
at nodes of ranvier
What are the three main factors that influence the movement of ions across the membrane?
Concentration of the ion on both sides of the membrane, the charge on the ion and the voltage across the membrane.
Why is the K+ equilibrium potential negative (e.g. -70mV) and the Na+ equilibrium potential positive(e.g. +40mV) when both are positive ions?
More K+ inside the cell than outside so tend to flow out of the cell, while more Na+ outside the cell than in, therefore tend to flow into the cell. A potential of -70mV is needed to attract K+ and stop net outward flow, while a positive charge of +40mV is needed to repel Na+ from entering the cell.
Which ion is important for the upstroke (rising phase) and which is important for the falling phase of the action potential?
In which direction do these ions move?
The upstroke mediated largely by Na+ ions moving down their concentration gradient into the cell. The falling portion of the action potential dominated by K+ ions moving down their concentration gradient and therefore exiting the cell.
What factors influence the speed of propagation of an action potential along an axon?
Larger diameter axons have lower resistance, so ions move faster – conduction velocity is proportional to the square root of the axon diameter.
There is a linear relationship between conduction velocity and myelin thickness
What does passive (graded) propagation result from?
local change in ionic conductance (e.g. synaptic or sensory that produces a local current) that spreads along a stretch of membrane becoming exponentially smaller
How would you describe AP?
they are regenerative
Action potentials propagate along an axon using nodes of Ranvier as “jumping points” - the process is called saltatory conduction
What influences conduction velocity? (2)
Axon diameter and amount of myelination
