Lecture 4 Flashcards
What is neuronal communication? What ions are important for it?
Neuronal communication relies on the movement of ions (charged atoms)
The two key ions necessary for neuronal communication are: Na + (sodium) and K+ (potassium). ALL communication is done through these two ions moving in and out of the cell.
Both these ions are positively-charged. When sodium ions enter the cell, they make the inside more positive. When potassium ions leave the cell, they make the inside more negative.
Membrane potential
They change the potential energy across the cell membrane, allowing neurons to transmit signals.
Always compare the inside of the cell to the outside!!(when an ion leaves the inside of the cell, then we say ‘the inside of the cell is more negative’ rather than ‘the outside of the cell is more positive’)
What is the resting membrane potential? Describe what happens when it’s disrupted
The resting membrane potential
Measures the difference between the voltage inside and outside of the cell. A healthy neuron has a resting membrane potential (voltage) of between -60 and -80 mV (this can fluctuate, but the comparison is often -65mV or -70mV)
The resting membrane potential needs to be maintained
It’s important for communication and signalling in neurons—it relies on electrical potential. When the potential is disrupted, it affects neuronal communication, creating issues w/ signal transmission and overall functon in neurons.
What proteins and mechanisms are involved in maintaining the resting membrane potential?
Resting membrane potential is balance of chemical and electrical forces. Only certain molecules/ions are permitted to cross the membrane, via channels and pumps.
AT RESTING POTENTIAL:
Na+/K+ pump is always working
K+ channel is always open
Na+ channel is closed at rest
Once sodium is out of the cell, it is stuck outside
Key processes:
Passive Diffusion when molecules move from high to low concentration naturally. No energy is needed. Passive diffusion can occur on its own but not to any meaningful extent.
Channels are proteins that allow specific ions (based on size, charge, etc.) through. Works through passive diffusion (along chemical gradient). A very fast way of moving ions. Limited by its reliance on natural forces to move ions.
Pumps are proteins that actively push ions against their chemical gradient (requires ATP energy). Is more mechanistic (double-door analogy). Slower way of moving ions—limited by need for energy.
Channels
Potassium-leak channels
“Leak” = Always open 24/7. Doesn’t use energy. Allows potassium to flow in and out, leading to net negative charge inside the cell—creates an equilibrium.
** Voltage-gated sodium channels**
Voltage-gated = opens at certain voltages. Opens at threshold of excitation—closed at resting potential.
3 states: closed, open and inactivated. As a ball and chain mechanism, auto-shutoff happens after 1ms using a ‘ball’ that blocks/inactivates the channel.
Stops rising state of action potentials.
Pumps
Sodium-potassium pump
Pumps 3 sodium ions out, and 2 potassium ions in the cell (more K+ is in the cell). Keeps net negative charge inside cell. Uses 2/3 of all brain energy to power these pumps. Located all over the membrane. Too slow to play a role in the AP!
Voltage-gated potassium channels
Open during the rising phase of AP for repolarization (when potassium channels open —> inside of cell is positive —> K+ goes out of cell). Slow to open and close—leads to hyperpolarization.
What are postsynaptic potentials?
Postsynaptic potentials = changes in membrane potential due to neurotransmitters binding onto receptors (postsynaptic side)
Can produce two effects:
EPSPs (excitatory post-synaptic potential) —> depolarization of the membrane at -70 to -67 mV., and the charge shifts towards 0mV (less negative). Increases likelihood of firing an action potential (AP). Typically occurs in dendrites.
IPSPs (inhibitory post-synaptic potential) —> hyperpolarization of the membrane at -70 to -72 mV, and charge moves further away from 0mV. Decreases likelihood of firing an AP.
Postsynaptic potentials are:
Graded: can be bigger or smaller depending on the number of neurotransmitters binded)
Rapid: very fast, travelling down the cell at the speed of electricity)
Decremental( decaying): PSPs travel like an electrical signal along an uninsulated wire
Large or small magnitudes
Very rapid at transmission
What are action potentials (APs) and where does it occur?
APs: a rapid all-or-nothing signal that travels down an axon when the membrane potential reaches -50mV
APs occur at the inital segment of the axon.
Lasts for a millisecond or two, and the signal strength is determined by how frequent it fires (APs are not graded—the size of every AP is always the same). Membrane potential in an AP changes from -70 mV to +55 mV.
Phases:
Threshold of Excitation: Voltage-gated Na+ channels open at the threshold, allowing ions to move across the membrane, generating the AP
Rising Phase (worse term: depolarization): Sodium (Na+) channels open, allowing Na+ ions to flow into the cell
Repolarization: Membrane potential returns to resting levels
Hyperpolarization (or repolarization): Membrane potential becomes more negative than resting
How can an AP go faster? What helps its conduction?
Myelinated neurons
Axons are covered in voltage-gated sodium (Na+) channels, facilitating rapid depolarization
Conduction speed is limited by the density of Na+ channels—like opening doors in a hallway, slowing down the signal (solution is not to spread them out—if Na+ channels are too sparse, the action potential can decay)
Myelin sheaths reduce the decay of the action potential, allowing wider spacing between Na+ channels. Faster conduction bc of fewer Na+ channels (fewer “doors”)
Dysfunction with myelin—Multiple Sclerosis (MS):
A disorder that progressively damages myelin, leading to lost conduction and weakened sensory/motor skills
Describe the axon terminal, and the effect of an action potential on the bouton
Terminal boutons
AKA“buttons”
The ends of axons where neurotransmission occurs
Contain vesicles filled with neurotransmitters
Action potentials and boutons
AP reaches terminal boutons —> Depolarization opens voltage-gated calcium channels —> Calcium influx makes vesicles release neurotransmitters into the synapse —> Neurotransmitters bind to receptors —> neuronal communication
The arrival of an AP depolarizes the terminal bouton because when voltage-gated calcium (Ca+) channels open, Ca+ flows into the bouton (since there’s 10,000x more calcium outside = BIG CHANGE). Increased calcium concentration makes vesicles to fuse with the bouton membrane—and then neurotransmitters spill into synapse and bind to receptors on PSN.
What are receptors? What kinds are there, and what do they do?
Receptors are proteins located on the surface of neurons that allows neurotransmitters to bind onto them and make cellular responses
Kinds of receptors:
Ionotropic Receptors:
Ionotropic —> they let in ions
AKA ligand-gated ion channels—which is usually closed but opens upon binding
Excitatory (depolarizes, EPSPs): More chloride outside the cell, negative, will flow inwards
Inhibitory (hyperpolarizes, IPSPs)
Fast, transient effect—effects immediately stop when the neurotransmitter is no longer bound
** Metabotropic Receptors:**
AKA G-protein-coupled receptors (GPCRs)—Not a channel (no hole to pass things through), and as extra proteins bound to them (G-proteins, activation molecules, signal molecules)
They help modulating the cell and modifying protein expressions (transcription and translation)
This process is slower, but causes long-lasting changes in the system
Cause signal cascades
Location of receptors:
Postsynaptic Receptors: Located on dendrites or cell bodies, receiving signals from other neurons.
Presynaptic Receptors: Located on axon terminals Autoreceptors: Monitors its own neurotransmitter release. Provides negative feedback—so it doesn’t release too many neurotransmitters
Heteroreceptors: Change how many neurotransmitters are released (changes the volume, but not the music itself). likely a third neuron at play that is receiving another neurotransmitter.
How does a signal end between cells?
Signal Termination:
Diffusion: Neurotransmitters can float away but may activate unintended receptors.
Enzymatic Degradation: Neurotransmitters are broken down into inactive metabolites.
Re-uptake: Neurotransmitters are recycled back into the presynaptic neuron for reuse, involving transporters and vesicular transporters.
