Membrane Potential/Action Potential Flashcards
What is membrane potential?
The difference in electrical charges across the plasma membrane - potential inside relative to extracellular solution
How do you measure membrane potential?
Measured using a microelectrode - fine glass pipette with tip diameter less than 1um penetrates cell membrane without bursting cell
What two factors must be present for establishment of a membrane potential?
Asymmetric distribution of ions across membrane (ion gradients)
Selective ion channels - primarily K, Na, Cl (also H, Ca), may be gated
In most cells, what ion channels dominate membrane ion permeability?
Open K+ channels
What is the effect of a K+ chemical gradient and electrical gradient that are opposite and equal?
No net movement of K+
Negative charge across membrane = resting membrane potential
If a membrane is selectively permeable for K+ then what will membrane potential be?
Membrane potential = Ek (K equilibrium potential)
If there are more K+ channels than Na/Ca channels then membrane potential is___________
Closer to Ek ~ -100mV
If there are more Na/Ca channels than K+ channels then membrane potential is___________
Closer to Ena or Eca ~ 0mV
What is depolarisation?
Decrease in size of membrane potential from its resting value (becomes less negative)
What is hyperpolarisation?
Increase in size of membrane potential from its resting value (becomes more negative)
What is the effect of increasing membrane permeability to a particular ion?
Membrane potential moves towards the Ei (equilibrium potential) for that ion
Opening what channels causes hyperpolarisation?
K+
Cl-
Opening what channels causes depolarisation?
Na+
Ca2+
What is conductance of a membrane?
How permeable a membrane is to a particular ion, dependent on number of channels for that particular ion are open
What is the Goldman-Hodgkin-Katz (GHK) equation used to work out?
The membrane potential of “real membranes” (take into account all channels in the membrane)
Give an example of mechanical gating
Hair cells in the inner ear, K+ channels close in response to membrane deformation, causes membrane depolarisation and ca2+ channels open. Results in vesicles containing neurotransmitter to fuse with the basement membrane (to afferent nerve). Neurotransmitter binds receptor on post synaptic plate - generates action potential to the CNS for interpretation
Where are synapses found?
Between: nerve cell - nerve cell
Nerve cell - muscle cell
Nerve cell - gland cell
Sensory cell - nerve cell
What dictates fast transmission at a synapse?
The receptor on the post synaptic membrane is an ion channel (neurotransmitter caused opening)
What do excitatory neurotransmitters cause at the synapse?
Opening of ligand gated channels that cause membrane depolarisation (Na, Ca) - “excitatory post-synaptic potential”
E.g acetyl choline, glutamate, dopamine
What do inhibitory neurotransmitters cause at the synapse?
Opening of ligand gated channels that cause hyperpolarisation (K+, Cl-) “inhibitory post-synaptic potential”
E.g glycine, GABA
What dictates slow transmission at a synapse? And give two examples?
The receptor and ion channel are separate proteins.
- Direct G protein gating - localised, rapid
- Gating bus intracellular messenger - throughout cell, amplification by cascade, slower
What things can also influence membrane potential?
Changes in ion concentration - most importantly extracellular K+ concentration - alters membrane excitability
Electrogenic pumps - e.g. Na/K ATPase adds one + charge out each time, contributes a few mV to membrane potential (more negative)
What does GABA do?
GABA works to open Cl- channels (in nerve cells) causing hyperpolarisation - has an inhibitory effect
How is the action potential “all or nothing”?
As the stimulus must cause depolarisation to reach threshold in order to cause action potential propagation. Also the action potential is the same size no matter how large the stimulus is (larger stimulus, more frequent action potentials)
What is the axon hillock?
Last part of neuron cell body that connect to the axon. The last site where membrane potentials propagated from synaptic inputs at summated before transmission to axon
What is the cause of the upstroke of the AP?
Due to large increase in permeability to Na, Na enters cell, depolarisation
What is the effect of reduced extracellular Na on upstroke of the AP?
Lower extracellular Na, less depolarisation when Na channels open, therefore smaller overshoot
How can you measure voltage currents?
Voltage clamps - used to measure the ion currents through membranes of excitable cells (at set membrane potential)
What are the differences in conductance of Na and K channels?
Na channels - show inactivation - inactivated very quickly after opening
K channels - don’t show inactivation, close much more slowly (return to MP slower) and remain Koenig after repolarisation causing hyperpolarisation
What allows inactivated Na channels to recover?
Hyperpolarisation of the membrane (inside of cell more negative) allows Na channels to become closed where they are excitable and open in response to a stimulus
What is the absolute refractory period (ARP)?
When nearly all of the Na channels are in the inactivated state therefore no matter how strong a stimulus is, an action potential cannot be initiated
What is the relative refractory period (RRP)?
Na channels are beginning to recover from inactivation and excitability returns towards normal as number of channels in inactivated state decreases, can initiate action potential if stimulus is strong enough
What are the main structural features of voltage gated Na channels? (5)
Single peptide subunit (containing 4 repeating domains)
Each domain has 6 TMS alpha helices
Between TMS helices 5 and 6 there is a pore region
TMS region 4 is positively charge
Between TMS helices 3 and 4 there is an inactivation particle
What does the pore region dictate?
Pore region dictates what ions can pass through the channel
What is the positively charged region of each domain for?
The positively charged region of each domain, causes a voltage field across the membrane (contributes to voltage sensitivity). When ion binds, causes conformational change and pore opens.
What is the function of the inactivation particle in VG Na channels?
The inactivation acts to block the channel pore, Na cannot enter pore
What are the main structural features of voltage gated K channels? (4)
Made up of 4 identical peptides (4 alpha subunits)
Each peptide subunit has 6 TMS alpha helices
Between TMS helices 5 and 6 there is a pore region
TMS region 4 is positively charge
What channels do local anaesthetics often act on?
Local anaesthetics act mainly by blocking VG Na channels therefore blocking depolarisation, therefore no action potential
(When channel open, more likely to become occupied by anaesthetic - block channel, pain decreases.
When axon diameter decreases, what’s the effect on conduction velocity?
Smaller axon diameter, slower conductance velocity
What is local current circuit theory?
The theory that depolarisation of a small region of an axon which spreads to neighbouring regions, depolarising them. Causes immediate local change. When Na enters cell, repels other + charges, attracts - charges, sets up local current
Depolarisation causes further (Na) channels to open thus propagating AP
What is the length constant (λ)?
Distance it takes ice the potential to fall to 37% of its original value
What is capacitance (Cm)?
The ability to store electrical charge - property of the lipid bilayer
What two things do spread of local current depend on?
Capacitance
Membrane resistance
What is membrane resistance?
Depends on the number of ion channels open
Lower resistance = more ion channels open = change in voltage spreads less far down axon
High resistance means what?
Less ion channels open
Local surround spreads further down axon
What’s the effect of axon diameter on travel of the action potential?
Wider the axon diameter causes local depolarisation to spread further
What is myelination?
Fatty, tightly packed membrane substance that surrounds the axon of some nerve cells. Formed of a Schwann cell. Forms an electricity insulating layer.
What are nodes of ranvier?
Gaps between myelin sheath, contain high density of Na channels
What is saltatory conduction?
the propagation of action potentials (depolarisation) along myelinated axons from one node of Ranvier to the next node (“jumps”).
Much faster, AP only at nodes (local currents depolarise next node to threshold, initiate AP)
How is conduction velocity proportional to diameter of myelinated and unmyelinated axons?
Conduction velocity is directly proportional to diameter of myelinated axon
Conduction velocity is proportional to the √diameter of unmyelinated axon
What is the maximum conduction velocity in myelinated and unmyelinated axons?
myelinated axons - max velocity ~120 m/s
unmyelinated axons - max velocity ~20 m/s
How does the myelin sheath improve conduction? (4)
Large increase in membrane resistance
Large decrease in membrane capacitance
Increase in the length constant
Slight decrease in time constant
Name two diseases that effect conduction of the action potential in the CNS
Multiple sclerosis (all CNS nerves, most common)
Devic’s disease (optic and spinal cord nerves only)
Name a disease that effects conduction of the action potential in the PNS
landry guillain barre syndrome
What do diseases that effect conduction of the action potential result from?
Breakdown/damage of the myelin sheath, show plaques of demyelination (autoimmune damage)
In regions of demyelination, density of action current is reduced because of resistive and capacitive shunting therefore depolarisation doesn’t reach next node of ranvier, threshold not met.
