WEEK 3 Flashcards
phospholipid barrier
hydrophobic membrane surrounding neurons, allowing the separation of aqueous ions between the extracellular and intracellular spaces. to move ions in and out, there are protein pumps (sodium potassium pumps) and ion channels (sodium channel or potassium channel).
two types of ion channels
1) leak channels: they are open and allow ions to passively flux up and down their concentration gradients
2) gated channels: closed at resting condition but open either due to electricity (voltage-gated channel) or neurotransmission (ligand-gated channel). once open, they allow ions to flux across the membrane
resting membrane potential: leak channels
negatively charged anions are permanently locked within the cell, making the intracellular space negatively charged. this attracts positive ions, sodium and potassium, towards the extracellular space. while also repelling negatively charged ions like chloride, the extracellular space is positively charged. in response to this charge, more potassium will enter the cell (as there are more potassium leak channels on neurons). some sodium will enter but there are less sodium leak channels.
resting membrane potential: sodium potassium ATP pump
energy-dependent mechanism that helps to maintain the high concentration of potassium in the cell, the low concentration of potassium outside the cell, the high concentration of sodium outside the cell, and the low concentration of sodium inside the cell. it collects 3 sodium ions from inside the cell and pumps them to the extracellular space. in return, 2 potassium ions are pumped into the intracellular space from the extracellular space. this maintains the concentration gradient at resting potential.
sodium potassium ATP pump: mechanisms
1) increases the concentration of sodium in the extracellular space
2) increases the concentration of potassium in the intracellular space
3) the exchange of positively charged ions helps to maintain the net negativity of the intracellular space compared to the extracellular space
two ionic forces
1) electrostatic force: the charge component, the one for the positive ions to go towards the negative ions through the leak channels
2) force of diffusion: they want to move along their concentration gradients from an area of high concentration to an area of low concentration (ex: potassium wanting to leave the cell due to lower concentration in the extracellular space)
ionic forces and the 3 main ions
1) sodium: both electrostatic force and diffusion want to push sodium into the cell - as the cell is negatively charged, and it has a low concentration of sodium. this makes sodium incredibly potentiated, meaning that as soon as a sodium channel opens, it will rush into the cell
2) potassium has divergent forces: electrostatic force attracts it to the negatively charged intracellular space, but the force of diffusion wants it out, since its in lower concentration in the extracellular space.
3) chloride ions shows the opposite to potassium: electrostatic force attracts it to the positively charged extracellular space, but the force of diffusion wants it in the cell, as its concentration is lower in the intracellular space.
equilibrium potential
point for any ion where the net flux across the membrane is 0, because of electrostatic force and force of diffusion being equal to each other. so under resting conditions, these ions would not move across the membrane potential.
graded potential
change in the membrane’s potential around the ion channel, which can be positive or negative. usually caused by the flux of sodium ions into the cell following the opening of a ligand-gated channel on the postsynaptic cell. if it is sodium or potassium it depolarizes the postsynaptic neuron (making it more positively charged towards the AP firing threshold). if it is chloride ions it hyperpolarizes the postsynaptic neuron (making it more negatively charged away from the AP firing threshold).
AP firing threshold
when the graded potential reaches the axon initial segment (AIS) there is a threshold which determines whether a consequent AP will be fired or not: if the graded potential is below the AP threshold, no AP is generated, it decays, and the cell returns to its resting potential. if the graded potential is above the AP threshold, an AP is generated and we get a rapid flux of sodium ions.
spatial summation of excitatory postsynaptic potentials (EPSPs)
if a single channel were to respond, that graded potential may not be above the threshold. however, if 3 inputs were to fire simultaneously, their responses would be summed in the cell body, so we have a much larger graded potential which travels to the AIS above the threshold and generates an AP.
temporal summation of excitatory postsynaptic potentials (EPSPs)
if a single input were weak, but was later followed up by a second input, alone neither of them would be able to match the AP threshold. however, if they fired very quickly after the other, their potentials would be summed up on top of each other and potentially lead to the firing of an AP.
excitatory postsynaptic potential (EPSP)
changes that happen in response to the positively charged ions (sodium and potassium) which moves the membrane potential towards the triggering threshold for an AP - depolarization.
inhibitory postsynaptic potential (IPSP)
changes that happen in response to the negatively charged ions (chloride) which moves the membrane potential away from the triggering threshold for an AP - hyperpolarization.
voltage gated channels (sodium and potassium)
1) voltage gated sodium channel: in response to electrical stimulus, the channel will open, and due to both electrostatic and diffusion forces, sodium will rapidly flux into the cell, depolarizing it.
2) voltage gated potassium channel: in response to electrical stimulus, the channel will open, and due to diffusion forces, potassium will flux out of the cell, rendering the intracellular space more negative - hyperpolarizing it.
action potential: phases
1) resting membrane potential
2) depolarizing stimuli
3) depolarization reaches the threshold: voltage gated sodium channels open and sodium enters the neuron
4) rapid flux of sodium further depolarizes the neuron
5) sodium channels close 0.5 ms after they open, so no sodium can flux in any longer
6) slower responding potassium channels open and potassium leaves the cell, hyperpolarizing it
7) voltage gated potassium channels close, some potassium enters the cell via leak channels
8) resurrection of the normal resting membrane potential
absolute refractory period
point at which the sodium channels are inactivated, they can’t flux sodium anymore. this lasts until the resting membrane potential has been restored. no AP can be triggered in that neuron. this has two functions:
1) allows the neuron to control its excitability
2) prevents back propagation
relative refractory period
after the hyperpolarisation phase, where potassium channels render the membrane potential more negative than the resting potential. during this time an AP can be triggered, but because the membrane is below resting potential, it would require a greater input.
channels’ three functional states
1) closed/resting state (sodium + potassium): when the gate is closed and can’t flux ions
2) open/active state (sodium + potassium): when the gate is open and can flux ions
3) inactive/refractory state (only sodium): a ball and chain mechanism has taken up into the pore and physically blocks it. although the gate is open, it is blocked, so no sodium can pass through and the cell can’t fire an AP.
sodium channel changes during an AP
1) resting condition: gate is closed
2) voltage-dependent activation of the gate: gate opens and sodium fluxes into the cell
3) depolarization phase: sodium moves the cell to a more positive state. if it is above the threshold, we get rapid opening of other sodium channels and a huge influx of sodium, with an even larger depolarization phase.
4) 0.5 ms after sodium gates are opened, the ball and chain blocks the gate, preventing further depolarization,
5) potassium channels open, pushing potassium outside the gate, and we have hyperpolarisation of the cell. the ball and chain is removed and the gate closes.
6) the channel is back to its resting condition.
myelin
generated by Schwann cells in the PNS or oligodendrocytes in the CNS. it is an insulating fatty layer that prevents the current from leaking across the environment.
AP conduction: non-myelinated axons
relatively slow process because sequential voltage-gated channels have to respond along the entire length of the axon.
AP conduction: myelinated axons
conduction is called saltatory conduction: the AP jumps from one node of ranvier to another. myelin can really exceed the speed of regular propagation because we don’t have to have sequential activation of ion channels across the entire length of the axon, we get saltatory conduction from one node to the next.
nodes of ranvier
bare uninsulated sections between the oligodendrocytes, exposed to the extracellular space. these are specialized compartments that have a high density of voltage gated channels, making them uniquely excitable.
synaptic transmission in chemical synapses
in response to an incoming AP, the calcium channels on the presynaptic neuron open. calcium floods into the cell and the vesicles move to the membrane via exocytosis, where they fuse with the membrane and are then released into the synaptic cleft. neurotransmitters will then diffuse across the gap and trigger the ligand-gated ion channels on the postsynaptic neuron.
stimulus-dependent neurotransmitter release
the firing mechanism between the presynaptic and postsynaptic cells is stimulus-dependent: the higher the voltage of the current, the more voltage-gated channels open, the higher the release of neurotransmitters, the more APs are triggered.
neurotransmitter removal: mechanisms
1) reuptake of neurotransmitters into the presynaptic cell
2) reuptake of neurotransmitters into supporting glial cells (astrocytes) - super energy efficient recycling
3) degrading of neurotransmitters on the postsynaptic membrane
4) diffusion of neurotransmitters away from the synaptic cleft and taken up into the blood stream
the 2s, 3r, 2d system
2 s:
- synthesis (presynaptic terminal)
- storage (presynaptic terminal)
3r:
- release (synaptic cleft)
- receptors (postsynaptic terminal)
- reuptake (presynaptic terminal)
2d:
- degradation (presynaptic terminal)
- drugs and disease
glutamate
amino acid widely distributed in the CNS, occurring at 70% of all synapses. there is very little glutamate at the PNS. it is the most important excitatory neurotransmitter in the CNS.
glutamate: synthesis
occurs in 2 types of cells:
1) glial cells: oxoglutarate is converted into glutamate by GABA transaminase
2) neurons: glutamine is converted into glutamate via glutaminase
glutamate: storage
stored in vesicles by a protein called the vesicular glutamate transporter (vGluT). to get glutamate in, hydrogen ions are pumped out of the vesicles. high hydrogen content makes vesicles acidic, and is used to pump in glutamate via a proton pump which converts the energy of ATP into higher concentration of hydrogen in the vesicle, which can then be exchanged for neurotransmitters.
glutamate: release
released by the nerve terminal at the axon terminal bouton. they are released in a calcium-dependent process: calcium is required to move and fuse vesicles with the membrane to allow neurotransmitters into the synaptic cleft.
