FHB Lecture 2: Cellular Excitability/ Neuronal AP Flashcards
Explain the different APs for the following types of vertebrate cells. What are the advantages of each type having such an AP?
Different shapes and duration are due to the specific ion channels expressed in each type.
Note: see how long the AP is for cardiac as opposed to the other types
What is a subthreshold signal?
Explain the relationship between subthreshold depolarization and distance?
Subthreshold signals FAIL to generate an action potential because they do not reach the threshold value. They generate linear responses. The subthreshold depolarization will decrease with distance. (The farther it travels away from where the signal originates, it will die off)
When is an action potential generated?
An AP is generated when an electrical signal surpasses the threshold signal for Na channel activation.
Subthreshold depolarizations are transmitted_______; these signals _____ with distance.
Subthreshold depolarizations are transmitted passively; these signals decrease with distance.
- What is the legnth/space constant (lambda)?
- What does the length constant depends on?
- The length/space constant is defined as the distance over which a subtheshold depolarization (local response) will spread and influence the next segment of a membrane… the distance over which the original response decays to approx 37% of the its original magnitude
- It depends on the ratio of rm to ra (membrane resistance to axial resistance)
- What are rm and ra?
- How do they affect the length constant?
- What does a bigger length constant mean for an axon?
1/2. Rm: Membrane resistance (rm) is the resistance of the membrane to allow electricity to travel from inside of the axon to the outside… the larger the Rm the larger the length constant
Ra: Axial resistance: resistance of the medium inside the cable. The bigger the ra the smaller the length constant
- A bigger length constant means the axon will conduct a signal for longer. The larger the lambda, the better off the axon because it will conduct a signal for much longer
Compare the length constant in two axons of different diameters. (one has a large diameter, one has a small diameter).
Comparison of length constant (λ) in two axons of different diameters.
- The larger diameter axon has a lower membrane resistance (rm) and a lower internal (axial) resistance (ra) than the smaller axon. However, ra decreases more than rm. As a result, an increase in diameter increases λ and increases conduction velocity.
- Where is myelin produced in the: CNS? PNS?
- What does myelin do to rm and legnth constant?
- Myelin sheath increases/decreases the membrane capitance (cm) therefore increasing/decreasing the rate of membrane depolarization.
- What is the internodal difference?
- Myelin is produced by: schwann cells in the PNS and oligodendrocytes in CNS.
Schwann cells wrap around axon except at nodes of Ranvier.
- Myelin increases rm and increases the length constant.
- Myelin sheath decreases the membrane capitance, therefore increasing the rate of depolarization. Thus, myelin significantly increases conduction velocity.
- Internodal difference is 1-2 mm
- Sodium channels are concentrated where?
- Explain “saltatory conduction”
- Explain how MS, and neuropathy type diseases relate to myelin? What kind of drug is used to pre-emptively treat those types of diseases and how does it work?
- Sodium channels are concentrated at the nodes of Ranvier
- Saltatory conduction: Na+ channels are concentrated at the nodes of Ranvier. Action potentials only occur at nodes and therefore appear to “jump” from node to node.
- Multiple sclerosis, diabetic neuropathies: destroy myelination and severely slow neuronal conduction. Treated with a pallative drug that blocks potassium channels, which increases rm, increases lambda, and increases the change of an AP reaching an area where it can still do its job
Describe the ionic current mechanisms responsible for neuronal AP.
The upstroke (depolarization phase) of the action potential is caused by a very rapid and brief (0.5 ms) increase in Na+ channel conductance. The repolarization of the action potential is caused by a delayed increase in K+ channel conductance along with the decrease in Na+ channel conductance (inactivation). K+ channel conductance is turned off (deactivates) by repolarization of the membrane potential. NOTE: the action potential always occurs between ENa and Ek.
The gating mechanism of sodium channels involves__________.
The gating mechanism of Na+ channels involves the physical conformation of the channel in three different states.
Explain the three different gating states for sodium channels: Resting, Activated and Inactivated.
Draw the picture.
Depolarization of Na+ channels is an example of what kind of feedback? (positive vs negative)
Depolarization of sodium channels is an example of positive feedback. Depolarization increases sodium permeability (which opens more sodium channels) which in turn causes further depolarization.
What is the basis for refractory periods?
The voltage dependent inactivation of Na+ channels is the basis for refractory periods.
Recovery from inactivation requires what?
Recovery from inactivation requires time, and and more negative membrane voltages (aka repolarization)
Define the relationship between resting membrane potential and Na+ channel activity.
At more positive resting potentials, Na channels become less available.
About 5% of Na channels are ready to party at -40 mV.
- Define Abolute Refractory Period (ARP).
- Define Relative Refractory Period (RRP)
- What are the refractory periods based on?
- Draw an AP and label which one is ARP vs RRP.
- ARP: the TIME during which a stimulus cannot ellicit a reponse aka AP
- RRP: the TIME during which a stimulus can ellicit a response
- In nerve (and heart), refractory periods are based on the voltage-dependent characteristics of Na+ channels. At more positive voltages, Na+ channels inactivate and therefore become unavailable for activation (absolute refractory period). As the membrane potential repolarizes, Na+ channels recover from inactivation (relative refractory period).
What is the normal extracellular concentration of potassium. Why is hyperkelemia so bad? What kind of pt’s are at risk for this.
Normal extracellular concentration of K is 4 mM/mEq
In hyperkelemia, the RMP becomes more positive, which causes Na channels to become inactivated/less available. The inward Na current decreases and conduction slows. (decreased excitability)
Signs and sypmtoms: slow mentation, muscle weakness
Pt’s at risk for this: dialysis pt, people who take hypertensive meds (ACE inhibitors)
Explain this diagram using words.
After an AP reaches a presynaptic button it induces membrane depolarization, which activates voltage gated calcium channels triggering Ca influx into the presynaptic site and inducing vesicle fusion and subsequent neurotransmitter release. NT diffuses in the synaptic cleft, activating ionotropic channels in the post-synaptic site. These channels then open and allow cation influx (excitatory) or Cl (inhibitory); this ionic current changes the membrane potential, eliciting a PSP.
EPSP vs IPSP: what kind of NTs are they caused by, what kind of ion do they let out, what do they do to the membrane, and do they increase or decrease likelihood of firing an AP?
EPSP: Excitatory Post-synaptic Potentials or EPSPs are caused by excitatory neurotransmitters (Ach, glutamate), allow cation influx and cause membrane depolarization (towards 0 mV), increasing the probability of firing an action potential.
IPSP: Inhibitory Post-synaptic Potentials or IPSPs are caused by inhibitory neurotransmitters (GABA, glycine), allow anion influx and (usually) cause membrane hyperpolarization (towards -65 mV), decreasing the probability of firing an action potential.
