Module 6 (ET neurons) Flashcards
Neurons
Nerve cells that are the principal building blocks and instruments of communication of the central and peripheral nervous systems; they receive information, digest it and respond to it by transferring it to other cells
Nervous system
PNS and CNS both form complex communication networks that allow an organism to interact in appropriate ways with its internal (contents of the body) and external (world outside the body) environments
Neuroscience
A scientific concerned with the function and structure of the nervous system
Communication
Electrical signals (dendrites cell body, axon) and chemical signals (synapses)
Structure of a vertebrate neuron
Vary in size and shape; soma (cell body), two types of processes - dendrites and axon(s) with axon terminals
RMP
Resting Membrane Potential; electrical potential difference across the cell membrane which results from separation of charge (carried by ions); can change during various stages of cell activity; more negative charges inside the cell compared to the EC fluid
Types of ion channels which affect the membrane permeability
Non-gated channels (leak channels that are open at rest); gated channels (voltage or ligand gated that are usually closed at rest)
RMP in neurons
Cytoplasm usually has a potential that is 50 to 70mV lower (more negative) than the potential of the extracellular space
Excitable substances
Only muscle fibres and neurons can suddenly respond with a transient change of potential (i.e. with an action potential) in response to a stimulus; other cells have a negative RMP but it doesn’t change when various stimuli act on them
What maintains the RMP
Unequal concentrations of Na+ and K+ outside the cell; unequal permeability of the cell membrane to these ions (the ratio of PK:PNa is about 40:1; due to concentration gradients, there is a steady diffusion of Na+ into the cell);
electrogenic action of the Na-K pump (Na/K ATPase); K+ and (to a smaller extent) Na+ non-gated channels
How are intracellular potentials measured
Microelectrode recording technique (pentration of the cell membrane) or patch-clamp technique (no penetration of the cell membrane)
Microelectrode recording technique
Penetration of cell membrane; glass capillary pulled so that its tip is very small; electrode is filled with electrolyte so it can conduct current and connected to an amplifier (voltmeter), second electrode is outside in EC space; allows measurement of PD between outside and inside
Patch-clamp technique
No penetration of cell membrane; glass electrode with a larger top seals to membrane between lipid bilayer; bridge forms a contact between what is inside the cell which allows measurement of potentials and current flow; fill pipette with electrolyte which creates an artificial inside
Concentrations of K+ and Na+ inside and outside neurons
K+: lower outside and higher inside (conc gradient out of cell)
Na+: higher outside and lower inside (conc graident in to cell)
Na/K ATPase pump
Maintains concentration gradients and RMP; cell is slightly permeable to Na+ gradient, so will gradually diffuse into cell along it; membrane highly permeable to K+ so they will escape; pump removes more positive charges (Na+) than introduces (K+) to the cell
Leak channels
Open at rest; in cell membrane of neurons, there are many leak K+ channels but very few leak Na+ channels (so they are much more permeable to K+ than Na+)
Gated channels
Voltage-gated (pd change); ligand-gated (chemical/ligand); mechanically-gated (shape change)
Equilibrium potential
Intracellular potential at which the net flow of ion is zero in spire of a concentration gradient and permeability; can be calculated for each ion by the Nernst equation
Nernst equation
Used to calculate the equilibrium potential for each individual ion that contributes to the RMP; does not require knowledge of the permeability of the membrane for the ion;
EK+ = 61.5mV x log ([K+]outside/[K+]inside)
ENa+ = 61.5mV x log ([Na+]outside/[Na+]inside)
When does the Nernst equation apply
In a situation when a cell membrane is permeable only to one ion (i.e. has leak channels only for one specific ion)
Rule 1
The higher the permeability of the cell membrane to a particular ion, the greater the ability of this ion to shift the RMP to its equilibrium constant
In neurons, the RMP is closer to the equilibrium constant for K+ because the membrane permeability is much higher to K+ than to Na+
Goldman equation
Method for calculating the value of the RMP by taking into account both the concentration gradients and the relative permeability of the resting cell membrane to K+ and Na+ ions;
Vm = 61.5mV x log (Pk[K+]outside + Pna[Na+]outside)/ Pk[K+]inside + Pna[Na+]inside)
Hyperpolarisation
Potential inside neurons becomes more negative; potential moves closer to the EK+ and away from the ENa+
Depolarisation
Potential inside neurons becomes less negative; potential moves away from the EK+ and closer to the ENa+
Action potential
Very brief fluctuation (short-lasting change) in membrane potential caused by a transient opening of voltage-gated ion channels (mainly K+ and Na+) which spreads along axon; occurs after the membrane potential reaches certain voltage called the threshold (depolarised)
Significance of an AP
Information is coded in the frequency of them; they can be regarded as a form of language by which neurons communicate; key element of the process of signal transmission along axons
Stages of an AP
Slow and graded depolarisation evoked by a stimulus; fast depolarisation; repolarisation; after-hyperpolarisation
Depolarisation to threshold AP
Stimulus causes a shift of membrane potential from the resting value to the threshold value; slow and graded depolarisation; strength of stimulus determines size of depolarisation
Fast depolarisation AP
Once threshold is reached, potential inside quickly shifts to a positive value which does not last long (overshoot; reversal of polarisation); sudden activation of voltage-gated Na+ channels which open very fast (PNa+ increases and PK/PNa = 1:20)
Repolarisation AP
Membrane potential goes back down to original RMP; Na+ channels inactivate and voltage-gated K+ channels open
After-hyperpolarisation AP
AHP; membrane potential goes down more negative than the original RMP before returning to normal; votage-gated K+ channels remain open for a while (PK/PNa = 100:1) and then close
Absolute refractory period
Fast depolarisation and repolarisation stages; time during AP when nerve cell is not excitable (after the stimulus evokes an AP, another stimulus would not evoke another AP within the same period - cell will not respond)
Relative refractory period
Hyperpolarisation stage; if a strong stimulus was applied, it may evoke an AP, however it is harder for stimulus to reach threshold because it is lower that RMP
Stimulus
Physical (electric current, light or mechanical stretch); chemical (drug or neurotransmitter)
Voltage-gated Na+ channels in AP
When voltage threshold is reaches, Na+ channels open and the ions move into the cell along both the concentration and electrical gradient; residues detect small changes in potential and will change configuration to open activation gates
Inactivation of voltage-gated Na+ channels
Slows down and then stops when the inside potential becomes positive (moves towards ENa+) and thus attracts Na+ ions less, and when Na+ channels inactivate; very important in nerve cells because they try avoid a large influx of Na+ ions which would depolarise the cell (losing the MP); this is when the inactivation gate changes configuration to block the channel
All-or-none
Each AP is an all-or-none event which is in contrast to the graded small subthreshold depolarisations or hyperpolarisations; amplitude of APs is usually constant and does not depend on the stimulus intensity
Evoking APs
Passing high current outside the nerve cell will evoke an AP under the cathode; the AP is not stationary and will move away from the point is is generated in both directions; the current will flow through the path with least resistance (outside the cell, which has no affect on excitability of membrane); across membrane and inside the axon only (can change RMP)
Rule 2
When the current generated by an outside source flows through the cell membrane from outside to inside, hyperpolarisation occurs; when it flows from inside to outside, depolarisation occurs
AP generation physiologically in CNS neurons
First generated in the axon initial segment (axon hillock) which has the lowest threshold (trigger zone); depolarisation to threshold evoked by EPSP which spread mainly passively from dendrites; once generated, APs are transmitted actively along the axon away from the cell body
Axon initial segment
Axon hillock where the potential threshold for APs is lowest due to the higher density of voltage-gated Na+ channels (more excitable); serves as the trigger zone for APs
EPSP
Cause a graident of potential which causes a flow of current that spreads along the dendrite and go through the membrane from inside to outside - depolarising the cell membrane; if it reaches threshold an AP will be generated and spread down the axon
Unmyelinated axons
Small diameter (~1um); transmission of APs is slow and continuous (form point to point)
Myelinated axons
Larger diameter (5-10um); transmission of APs is fast and saltatory (in large steps; discontinuous) and disrupted at nodes of Ranvier; oligodendrocytes in CNS and schwann cells in PNS (types of glia cells)
Two stages of AP transmisison
Occurs in both types of axons; all about electricity (flow of ions) and therefore the flow of current
- Passive spread (of current)
- Generation of APs
Passive spread of current
Subthreshold (has not reached the threshold) depolarisation at one region of the membrane; passive current flow (inside and outside the axon); depolarisation of adjacent parts of a membrane
How far can current spread passively
Over a short distance; local (subthreshold; not activated voltage-gated channels) depolarisation induced by current injected into an axon by a glass microelectrode - AP gets smaller because some ions dissipate very quickly as it flows along axon
AP transmission in unmyelinated axons
AP generated and a passive current flows (fast); depolarisation of adjacent parts of the membrane to threshold; voltage-gated Na+ channels in adjacent parts of the membrane open and a new full size AP is generated in these adjacent parts of the membrane - which takes time and so conduction velocity is very slow
What does myelination do
Increases the AP conduction velocity by increasing the efficiency of passive spread of current; due to their insulating properties, there is less current dissipation as it flows along the axon, so they do not need to be regenerated at every part of the axonal membrane
Saltatory conduction
Process of AP transmission in myelinated glia cells; APs generated at nodes of Ranvier and current flows passively between nodes
Generation of AP in sensory neurons
Stimulus acting on receptors in sensory neurons does not immediately evoke APs; evokes a graded depolarisation in the sensory endings (receptor potential) which spreads passively to the nearby located trigger zone; APs spread along the axon toward the CNS
AP only conducted in one direction
Under physiological conditions, only in one direction; the passive current flowing backwards is unable to reactivate the voltage-gated channels because they are in the absolute refractory period; by the time the ARP is over, the AP has moved down the axon
Sensory neurons
PNS contains axons of sensory neurons; would be connected to sensory neurons in the skin and transmit information to the CNS; also have some in internal organs
Strength of stimulus
Information encoded in the amplitude of the receptor potential and the frequency of APs
Sensory neuron structure
Distal: trigger zone and connection to muscle fibre
Proximal: synaptic terminal and sensory neuron cell body
Synaptic transmission
Communication between neurons within the CNS in the brain or a neuron and muscle fibre; usually very fast process of transferring information between neurons or between neurons and muscle fibres; can occur through chemical or electrical synapses
Neuromuscular junction
End plate; peripheral synapses
Stages of synaptic transmission
- Arrival of an AP from a cell body of a motor neuron is transmitted to the pre-synaptic terminal
- voltage-gated Ca2+ channels open, influx of the ions from outside to inside (due to increased presynaptic Ca2+ permeability)
- release of transmitter by exocytosis which is stored in synaptic vesicles, into the synaptic cleft
- reaction of transmitter with postsynaptic receptors
- Activation of ligand-gated ion channels (K+ and Na+)
- Movement of ions leads to the depolarisation of the postsynaptic membrane; EPP and AP
Main types of chemical synapses in the CNS
Excitatory: depolarisation of the postsynaptic membrane (EPSP)
Inhibitory: hyperpolarisation of teh postsynaptic membrane (IPSP)
Key features of a chemical synapse
Specificity: specific NTs have specific effects on the postsynaptic membrane
Complexity: type, time course, strength, location, timing
Plasiticity: changes in synaptic structure and function associated with development, agening and learning
Neurotransmitters
Chemical messengers that open or close ion channels and lead to the depolarisation or hyperpolarisation of postsynaptic membrane; can bind to many different types of receptors, each of which produce a different affect on the neuron function
EPSP
Excitatory postsynaptic synapse potential; neurotransmitters include glutamate, or ACh; open channels selective for K+ and Na+ (sometimes Ca2+), shifts the RMP towards threshold for generation of AP (depolarisation)
IPSP
Inhibitory postsynaptic synapse potential; neurotransmitters include GABA or glycine; open K+ channels, hyperpolarises the membrane
Direct gating
When the transmitter binds to the receptor/ion channel complex, causing the pore to open and ions to pass through, depolarising or hyperpolarising the cell membrane; very fast and short lasting
Indirect gating
When the transmitter binds to receptors, activating a biochemical pathway involving a G-protein; these bind GTP when activated by a membrane receptor and leads to the production of secondary messengers (cAMP); secondary messengers activate activate protein kinases which phosphorylate specific ion channels leading to hyperpolarisation/depolarisation of membrane ; effects are slower and longer lasting
Small molecule neurotransmitters
Classical NTs, usually fast action and act directly on postsynaptic receptors; amino acids, acetylcholine, amines
Neuropeptides
Neuromodulators; large molecule chemicals that have an indirect action on postsynaptic receptors, or modulatory action on the effects of other NTs; slow and usually more diffuse action; neuropeptide Y (NPY), substance P, kisspeptin, enkephain
Factors determining synaptic action
Type of NT; type of NT receptor/channel complex expressed in the postsynaptic membrane; amount of NT receptor present in the postsynaptic membrane
Glutamate
Main excitatory NT in the CNS; binds to 3 main glutamate receptors which are directly gated ion channels (AMPA, NMDA, Kainate); each have different permeabilities to glutamate and different functions
Excitotoxicity
Too much glutamate (activation of NMDA receptor) causes entry of Ca2+ and can damage/destroy the cell, leading to a stroke, epilepsy and traumatic brain injury
NT inactivation and recovery after release
Diffusion (NTs removed from the synaptic cleft to some degree by diffusion)
Enzymatic degradation (in the synaptic cleft by certain enzymes)
Re-uptake (and re-cycling; act on postsynaptic receptors and then are transport back to where they were released)
Integration of synaptic inputs of neurons
Each neuron recieves thousands of synapses (IP and EP); each of these, when activated, produce only very small postsynaptic potentials at the axon initial segment; in order to depolarise the initial segment to threshold, EPSPs need to be enhanced
Temporal summation
Occurs when a high summation of APs in the presynaptic neuron elicits postsynaptic potentials that summate each other; can occur between individual EPSPs; can enhance the duration and amplitude of IPSPs
Spatial summation
Effect of triggering an AP in a neuron from one or more presynaptic neurons; occurs when more than one EPSP originates simultaneously and at a different part of the neuron; can occur between individual EPSPs; can enhance the duration and amplitude of IPSPs
