Neurotransmission Flashcards
Action potentials
allow the membrane changes to be conveyed over long distances (e.g. from the tip of your toes to your spinal cord) because they allow regeneration (preventing the signal generation that would occur if the only forms of change in membrane voltage were graded potentials).
- Once Vm reaches the AP threshold, the cell will depolarize in a manner that is independent of the initiating stimulus
- All-or-none DOES NOT mean that all action potentials are the same size or shape—either in different neurons or on the same neuron at different times (see refractory period for an example of this)
- Multiple action potentials occur in spike trains: sequences of APs that encode information
stages to an AP
0: Resting membrane potential: the RMP fluctuates, as graded potentials (especially EPSPs and IPSPs) depolarize and hyperpolarize the membrane.
1: A sufficiently large depolarizing event allows the membrane potential to reach the threshold (2) for an action potential to occur (basically, an AP is triggered by a graded potential or a summation of several graded potentials)
2: AP threshold: the trigger point where depolarization causes a rapid depolarization that can’t be interrupted once it starts. The AP threshold is typically between -40 and -60 mV
3: Rising phase (depolarization)
4: Peak: an action potential’s depolarization generally reaches a maximum between 0 and +40 mV
5: Falling phase (repolarization)
6: Afterhyperpolarization (undershoot): the membrane potential recovers to a value more hyperpolar than the membrane potential (~-85 mV), before recovering to the RMP (0).
channel activity during an action potential
An action potential is triggered by a graded potential that causes the membrane to depolarize until it reaches the threshold for activation of voltage-gated Na channels. Opening of these channels causes a rapid depolarization. When the voltage-gated Na channels inactivate and voltage-gated K channels open, the action potential peaks. Vm then depolarizes, overshoots the resting membrane potential, as the voltage gated K channels stay open. When these channels close, the Vm returns to the resting potential.
Ionic basis during an AP
Threshold (2) and rising phase (3)
• explained by the properties of the voltage-gated Na+ channels
o activation gate opens at ~-40 mV
o opening of Na+ channels depolarizes the cell
o depolarization will cause the opening of more voltage-gated Na+ channels (called a positive feedback or regenerative progress)
Falling phase (5) and Afterhyperpolarization (6) • explained by the properties of delayed rectifier K+ channels (one type of voltage-gated K+ channel) o activation gate opens around 0 mV→ delayed opening relative to voltage-gated Na+ channels→ K+ leaves the cell→ repolarization toward Ek (~-88 mV) o no inactivation gate→ channels close randomly after some period of time→ channels stay open even though the membrane has repolarized to the RMP → afterhyperpolarization
Why is the AP peak (4) NOT ENa (+60 mV)?
1) Voltage-gated Na+ channels inactivate (functionally close)
2) Large number of open channels decreases membrane resistance and the electrical driving force is less as the membrane potential nears the Na+ equil. Potential→ voltage change caused by the sodium current is not as large at positive voltages as it is between -40 and 0 mV
3) Chloride channels become more influential (remember that they do not have much effect at the resting potential because ECl is ~=RMP)→ Cl- ions enter the cell and hyperpolarize the membrane
4) Voltage-gated K+ channels activate
➢ Na+ channel inactivation would be sufficient to create the peak (i.e. Na+ channel inactivation begins the repolarization phase; K+ channel activation completes it
Graded potentials
- proportional (meaning amplitude decreases with distance)
- bidirectional (travel passively)
- can be integrated both temporally and spatially
- don’t require VG channels
Propagation:
Three primary forms:
1) receptor potentials occur in specialized sensory receptor cells
2) post synaptic potentials occur in neurons
— result from the activation of ligand-gated channels
— depolarizing are called excitatory postsynaptic potentials (EPSPs)
— hyperpolarizing are called inhibitory postsynaptic potentials (IPSPs)
— the ionic basis of post synaptic potentials is under neurotransmission
3) end plate potentials (EPPs) occur in muscle cells (activation of ligand-gated channels)
Action potentials
- all or none
- larger
- unidirectional
- have salutatory conduction (“jumping” from node to node)
Propagation:
- inward Na+ currents that occur during the rising phase of an action potential spread through the interior of an axon in a manner analogous to a graded potential
- these currents will depolarize an adjacent area of membrane, causing it to reach AP threshold and open the VG Na+ channels in that region
o because the VG Na+ channels produce a regenerative current, the AP retains its amplitude with distance (it’s “all or none”) as subsequent patches of membrane are activated
- AP propagation is facilitated by myelination because:
o VG Na+ channels are concentrated at the nodes
o The myelin insulates the axon, preventing ions from leaking out and therefore has high resistance)
- As a result, the spacing between the nodes is critical; if they are too far apart, the currents will decay to the point that they are not large enough to depolarize the membrane at the next node )
o In unmyelinated axons, the VG channels must be spaced frequently enough to ensure current carried is large enough for conduction
• Refractory periods
• “All-or-none” principle: the amplitude of the change is independent of input
• Refractory periods
o Absolute: the period of time when the majority of VG Na+ channels are inactivated when no amount of depolarizing current can cause an action potential
o Relative: as VG Na+ channels transition from the inactivated to the closed state (i.e. they become capable of being activated), the membrane becomes capable of supporting a 2nd action potential
— During the relative refractory period it takes a larger than normal depolarization to produce the 2nd AP because
1) the membrane is hyperpolarized during the afterhyperpolarization
2) the large number of open channels decreases the membrane resistance, requiring more current to produce the same change in membrane voltage
— the peak of the AP will be lower in amplitude than normal
• this does not violate the principle of “all or none” which says that an AP will either occur or it won’t
• “all or none” doesn’t say anything about the amplitude of the AP!
• Conduction velocity
: the speed with which an AP propagates down an axon
• Conduction velocity is based on diameter and degree of myelination.
o Slower in small diameter fibres due to an increase in axial resistance
o Faster in myelinated fibres due to an increase in membrane resistance
o The membrane potential change within an axon (i.e. between locations that have voltage-gated channels like Nodes of Ranvier) is governed by the same forces that apply to graded potentials
• Differences in the conduction velocity explain the response to local anaesthetics.
conduction velocities of various neurons
fastest: myelinated: Aa Motor AB sensory AGamma sensory B autonomic
unmyelinated:
C sensory
1) Electrical synapses
- Direct electrical coupling between two cells
- Mediated by gap junctions which are pores constructed of connexin proteins
- Essentially result in the passing of a graded potential (EPSP or IPSP) between two cells
- Very rapid (no synaptic delay)
- Passive process→ signal can degrade with distance→ may not produce a large enough depolarization to initiate an AP in the postsynaptic cell
- Bidirectional (i.e. a post synaptic cell can send a message to a pre synaptic cell)
2) Chemical synapses
- Slow
- Active (require ligand-gated channels)
- Pseudo-unidirectional
safety factor
➢ The probability that a presynaptic AP will produce a postsynaptic AP is termed the safety factor.
➢ Neither electrical or chemical synapses are perfectly secure
➢ Many central synapses fail more than 50% of the time
➢ The neuromuscular junction may be the most secure synapse; in health people, the safety factor of that synapse is >50%
- Identify the steps in chemical neurotransmission,
NT release
Receptor Activation
Active Termination
1) Neurotransmitter release
• NT release from the presynaptic terminal consists of a series of steps
a) Depolarization of the terminal membrane
b) Activation of VG Ca2+ channels
c) Ca2+ entry (the amount of Ca2+ that enters the terminal is extremely dependent upon the amplitude and shape of the action potential→ an exception to the idea that all APs are created equal)
d) A subsequent release of neurotransmitter into the synaptic cleft (resulting from a conformational change in specific proteins in docked synaptic vesicles that will fuse with the plasma membrane)
e) Vesicle fusion causes NT to spill into the synaptic cleft and diffuse towards the receptors on the postsynaptic cell
• The NT release mechanisms are disrupted in several diseases and by some biological toxins
