Lecture 1 - The Action Of Drugs On Nerve Cell Function 1 & 2 Flashcards
Why is the Na-K ATP-are pump referred to as an electrogenic pump?
Creates a charge disparity (between the outside and inside of the membrane)
Why do ions need specific ion channel?
(Charged) ions cannot pass through the phospholipid bilayer, due to the hydrophobic (fatty acid) tails
Specific ion channels (proteins) create hydrophilic pathways for ions to pass through
Why are Na+ ions used in the generation of APs?
Because at membrane potential (-70mV), Na+ is out of equilibrium (ENa = +30mV)
Therefore Na+ ions will want to flow into the cell down the conc / electrical gradient
Where does the Na+K+ ATP-are pump get its energy from?
ATP hydrolysis
Where does depolarisation occur in myelinated neurones?
Nodes of Ranvier
What should be the target of drugs for MS (multiple sclerosis) and why?
Blocking K+ channels
In MS, you want to PROLONG the duration of the AP (i.e. depolarisation) to give more chance of the AP jumping across the plaque
Do this by blocking K+ channels that cause repolarisation
What provides connectivity in the NS?
Neural networks
What structures protect the CNS?
Brain - skull
Spinal cord - vertebral column
What is used to record electrical activity of the brain?
Electroencephalograms (EEG)
What is the purpose of keeping Na+ ions out of equilibrium across the cell membrane?
Resting membrane potential = -70mV
(Inside of the cell is more negative than the outside)
Maintained by selective permeability of cell membrane to different ions and the Na+/K+ pump
The Na+ ion concentration is much higher outside the cell than inside, and this concentration gradient tends to drive Na+ ions into the cell. However, the cell membrane is relatively impermeable to Na+ ions, which are prevented from freely entering the cell by ion channels that are mostly closed at rest.
By keeping the concentration of Na+ ions out of equilibrium across the membrane, the neuron is primed to generate an action potential when the appropriate stimulus is received. When the neuron is stimulated, ion channels open, allowing Na+ ions to rapidly flow into the cell, depolarizing the membrane and generating an action potential.
Thus, by maintaining an unequal distribution of Na+ ions across the membrane, the neuron is able to generate and propagate action potentials in response to appropriate stimuli, allowing for proper communication between neurons and other cells in the body.
What is the normal direction of an impulse in a neurone?
From the… to the …
From the SOMA to the AXON TERMINALS
What is the net gradient (and movement) of K+ ions?
K+ ions move out of the cell down the CONC GRAD - bc there’s greater [K+] inside the cell than outside
K+ ions move into the cell down ELECTRICAL GRAD - bc +ve charged ions are attracted to net -ve charge inside the cell
The conc grad > electrical grad = net movement of K+ ions OUT of the cell
What is the net gradient for Na+ ions?
Na+ ions move INTO cell down conc & electrical gradients
Net gradient INTO cell
What is the Nernst / Equilibrium potential for Na+?
ENa = (RT/zF).ln([Na]o/[Na]i)
ENa ~ +30mV
What is the intracellular concentration of organic anions (A-)?
130mM
(These don’t have ion channels)
What is the function of the NS?
Acts as a communications network
Receives sensory info
Initiates actions - i.e. hormone release / muscle contraction
What is the function of neurones?
Communication / memory
What is the function of glia?
Support / communication
What is the equation for the Nernst / Equilibrium potential of K+?
Ek = (RT/zF).ln ([K]o/[K]i)
Ek~ -70mV
(Approximately equal to [resting] membrane potential)
Explain the variables in the Nernst / Equilibrium potential
Ex = (RT/zF).ln ([X]o/[X]i)
R = gas constant
T = temp (K)
z = valency of ion (Na+ / K+)
F = faraday constant
[X]o = conc X+ outside the cell
[X]i = conc X+ inside the cell
Explain the Nernst / Equilibrium equation
The Nernst equation is a mathematical formula used to calculate the equilibrium potential for an ion across a membrane.
It tells us the electrical potential required to balance the conc gradient of an ion across a membrane. At equilibrium, the electrical potential generated by the conc gradient is equal and opposite to the membrane potential, resulting in no net movement of the ion across the membrane.
If the membrane potential of a neurone is more + than the equilibrium potential, then ions will tend to move INTO the cell. If the membrane potential of a neurone is less + than the equilibrium potential, ions will tend to move OUT of the cell.
What is the difference between myelinated and unmyelinated neurones?
Myelinated neurones - axon is insulated by the myelin sheath - made up of several Schwann cells wrapped around the axon.
This prevents ionic leakage and therefore conduction is faster as impulses ‘jump’ between the Nodes of Ranvier in saltatory conduction
What are the nodes of Ranvier?
Sections of axon without myelin sheath, bathed in external fluid
What is the CNS made up of?
The brain and spinal cord
What happens to the net gradient of K+ ions over time (generation of membrane potential)?
Over time, the inc movement of K+ ions OUT of the cell decreases [K+] inside the cell
Electrical gradient gets stronger as the inside of the cell gets more negatively charged
Concentration gradient gets weaker as there is less difference between the intra & extracellular ion concentrations
This occurs until the gradients are equal, equilibrium is reached and there is NO NET MOVEMENT (or gradient)
This is membrane potential (-70mV)
What does the somatic NS control?
Skeletal muscle contraction (limbs)
What does the sensory NS control?
Skin
Viscera - i.e. heart, kidneys, gut
What does the Na+/K+ ATP-ase pump do?
Pumps 3Na+ OUT of the cell
Pumps 2K+ INTO cell
Generating an overall -ve charge inside the cell
What does the autonomic NS control?
Involuntary actions
(E.g. HR / BP / digestion / filtration of blood kidneys)
What controls ion movement across the neuronal cell membrane ?
Voltage-gated ion channels that span the membrane
What causes MS (multiple sclerosis?)
Damage to the myelin sheath
Therefore APs cannot ‘jump’ across Nodes of Ranvier
Causing transmission failure
What are the intracellular & extracellular concentrations of Na+ ions ?
Intracellular = 10mM
Extracellular = 120mM
= net movement INTO cell down conc gradient
What are the intracellular and extracellular concentrations of K+ ions?
Intracellular = 125mM
Extracellular = 5mM
= net movement OUT of the cell down conc gradient
What are the intracellular & extracellular concentrations of Cl- ions
Intracellular = 5mM
Extracellular = 125mM
= net movement INTO cell down concentration gradient
What are the 4 stages in the generation of an AP?
- Resting / membrane potential ~ -70mV
- Stimulus causes DEPOLARISATION, influx of Na+ ions increases membrane potential to above threshold (-50mV)
- Action potential generated (~ +30mV)
- K+ ion channels open, K+ ions move out - REPOLARISATION (decreases membrane potential)
- Membrane repolarises below membrane potential - HYPERPOLARISATION - ensures discrete impulses
- Return to resting / membrane potential
What are the 3 main divisions of the PNS?
- Somatic NS
- Sensory NS
- Autonomic NS
What are the 2 phases of inactivation?
- Absolute - nothing will open the channels
- Relative - if you increase stimulus activity, some action potential will fire
What are the 2 major cell types in the NS?
- Neurones
- Glia (Neuroglia)
What are the 2 gradients generated by ions?
- Concentration gradient
- Electrical gradient
What are the 2 divisions of the autonomic NS?
- Sympathetic - increases HR / BP
- Parasympathetic - decreases HR / BP
What are the 2 different types of glial cell in the CNS & PNS?
In CNS - oligodendrocytes
In PNS - Schwann cell
What are some symptoms of multiple sclerosis (MS) caused by transmission failure of action potentials?
Difficulty breathing / moving
Eye problems
What are the names of 2 K+ channel blockers (drugs) used in the treatment of MS?
4,aminopyridine
Tetraethylammonium (TEA)
If you stimulate an axon directly, can action potentials travel up and down an axon simultaneously?
Yes
How is the electrical gradient generated?
+ve charged ions are attracted to region of net -ve charge inside the cell
How is the concentration gradient generated?
By a difference in concentration of ions across a membrane
Ions move down the concentration gradient from a region of high(er) to a region of low(er) concentration
How are ion gradients established ?
Na+/K+ pump
Pumps 3Na+ OUT
Pumps 2K+ IN
Generates electrical & concentration gradients
How do ions move across cell membranes?
In response to gradients
Through specific ion channels
How do action potential communicate sensory info to cells?
The frequency of the action potential
*it is not the amplitude - All-or-Nothing principle (AP must reach above threshold)
Describe the states of the Na+ & K+ channels at resting membrane potential (-70mV)
Both K+ and Na+ channels closed - K+ ions can’t leave the cell, Na+ ions can’t enter the cell
Na+ channel ready for activation - inactivation gate is open
Describe the states of the K+ and Na+ ion channels at repolarisation
SODIUM INACTIVATION - Na+ channel inactivation gate closes, preventing Na+ ions moving into the cell
K+ channels open - K+ ions diffuse out of the cell
This decreases the positive charge within the cell = repolarisation
Describe the states of the K+ and Na+ channels in hyperpolarisation
Na+ inactivation gate shut, K+ channels open
This allows for the loss of excess +ve charge
Providing some level of control over the frequency of AP firing and ensuring that impulses are discrete
Describe the states of the K+ and Na+ ion channels at depolarisation
Na+ channels are open (both activation & inactivation gates) - causing an influx of Na+ ions into the cell - causing depolarisation
K+ ion channels closed - preventing loss of +ve charge
After arriving at nerve terminals, can APs reflect back along the axon to the soma?
No because the section of membrane that it has just travelled along will be undergoing the ‘refractory period’ due to hyperpolarisation
This makes it harder for an action potential to be generated, ensuring that the impulses are unidirectional
