Action Potential (aka. Electrodiffusion III) Flashcards
Was ist den “hopping over barriers” model?
- Beschreibt die Ionenbewegung in Proteinen
- Keine Kontinuierliche Diffusion
- Definierte Ionenbindungsplatte
- Ion channels as tubes with defined internal spaces for the ions to stop!
- an enzyme kinetic approach to ion permeation
- Durch Anlegen eines E- Feldes wird die Energiebarriere herabgesetzt auf eine Seite während auf der andere erhöht.
What is the hydration Energy?
- The hydration energy (delta)H is the stabilization gained by orienting water molecules appropriately and polarizing their electron clouds in the intense local field of the ion.
- the stabilization of an ion by water is strong and stripping water from the ion needs a lot of energy.
- DH (H+) = - 269 kcal/mol), DH (Na+) = - 105 kcal/mol), DH (K+) = - 85 kcal/mol)
How do selective Ion channels work?
SELECTIVE ION CHANNELS
- 5A pore diameter
- ions must be dehydrated. This dehydration occurs within roughly 1 ns.
- ==> the water is replaced by chemical groups belonging to the pore that provide a nearly perfect mimic of the geometry of water.
What are the elementary properties of a short pore?
- Resistance within the pore
- Two components of access resistance of the path converging to the pore.
- The voltage accross the membrane = TEST POTENTIAL
- when the test potential is small and the ion concentration in the medium is high => Ohms law!
- If the test potential is large, the current in the pore might demand more ions than the neighbouring solution may provide. Thus, if there are not enough ions, the current is reduced due to a local depletion
Describe the crowded conditions in narrow pores and what does water in the pore bewirkt?
If pore is not much larger than the Ion diameter
- Ions only move in one direction
- For n Ions, this reduces their mobility in the pore by a factor 1/n
Water in channels lead to flux coupling between Ion flow and water movement.
- Streaming potential= If water is forced by hydrostatic or osmotic pressure, the ions move with it
- Electro osmosis= If current is forced to flow by an applied voltage, the ions will drag water along too.
Beschreiben Sie was im Bild zu sehen ist & Nenne Sie die dazu gehörigen Komponenten.
K- Potassium /Kalium Ion
- rot: selectivity filter –> Carbonyl oxygens
- grün: K ionen
–> The carbonyl oxygens in the selectivity filter (red stick ends) provide almost identical geometry to the waters of hydration (red spheres) around the potassium ions (green, 1-4). Therefore, there is not a big energy barrier to enter the filter, where the ions must be dehydrated
Why use electrical signaling?
SPEED and BANDWIDTH
Welche wären anderen Optionen zur Reizweiterleitung und wie so sind die nicht geeignet?
- Diffusion: 39 W
- Molec. Motors: 4,5 Std
- Blutplus: 200 ms
- AP : 40 m/s = bis zur 150 m/s
Alle sind viel zu langsam!!
Beschreiben Sie den Hodgkin-Huxley Model und
- to explain the ionic mechanisms underlying the initiation and propagation of action potentials in the squid giant axon.
- treats each component of an excitable cell as an electrical element
RESULTS
- They found that the axon had a resting potential of around –60 mV.
- When the local cell membrane potential went above ~ –40 mV, an action potential fired.
- they saw that sodium (Na) channels activate with a cubic dependence m3 (suggesting 3 particles) and inactivate with a linear dependence h (a single inactivation particle).
- potassium (K) channels activate slowly with an n4 dependence (4 particles).
Explain the structural biology & gating particles of Na-channels.
Beschreiben Sie die saltatorische Erregungsleitung
- AP jmps along between Ranvier Nodes
- Mylein ( Oligodendrocytes or Schwann cells) wraps the axon and:
- reduces Capacitance
- increases Resistance to the outise ( 1:100)
- increases conduction speed
- reduces membrane time constant
If the leak conductance is non-selective, what is EL, the leak current reversal potential in the Hodgkin-Huxley model? Does the leak current reduce or increase the resting potential? [reducing would be a lower value, not a more negative value]Non-selective leak has EL = 0 mV. Such a leak conductance tends to reduce the membrane potential (bring it closer to 0 mV).
Non-selective leak has EL = 0 mV. Such a leak conductance tends to reduce the membrane potential (bring it closer to 0 mV).
Let’s compare a myelinated and non-myelinated axon of arbitrary length. If the node:internode length ratio is 1:99, and the internode capacitance is 10% of the node capacitance, calculate the energy saving due to myelin.
The non-myelinated axon has capacitance C (per unit length).
We assume the node has the same capacitance per unit length as the unmyelinated axon. The myelinated axon has capacitance (0.01 * C) + 0.99 (C/10) = 0.109 C The energetic cost can be estimated by considering the charge required to bring each axon potential to its peak voltage. No matter how we calculate this, we know that Q = V.C holds (charge is voltage times capacitance) and the voltage is the same in each axon. We will need to put back all the Na+ ions that are used, using ATP. Therefore, the ratio of the energetic costs are the ratio of the capacitances, therefore the energy saving for the axon alone is 1 – 0.109 = 89.1%. About 10 times more efficient.
NB the myelin itself uses energy, and therefore, overall, the most important role of myelin is to make nerve conduction faster.
Recalculate the GHK voltage Erev with the same numbers as in the script, but add chloride. [Cl]in = 10 mM, [Cl]out = 110 mM. Can you change the membrane potential by opening Chloride channels (changing PCl)? What do you have to do to make chloride more effective? (Consider making a spreadsheet where you can alter P and [Ion] )
Compared to the normal resting condition, with PNa = 0.05 PK (Potential = – 64 mV, see script), the membrane potential barely changes with these chloride conditions, irrespective of the chloride conductance. That’s because ECl is around –62 mV. Therefore, to allow for more hyperpolarisation, the cell must pump out more Cl ions and reach a lower internal chloride and greater gradient. If Clint is halved to 5 mM, then ECl is –80 mV and PCl = PK = 20 PNa gives Erev = –71 mV and changes in PCl easily alter the membrane potential.
*** The bigger the gradient, the bigger the effect of conductance change. ***
What are the cost of signaling?
Steps in the AP
- Resting membrane potential
- Depolarising stimulus
- Dep. Membrane goes to threshold –> Voltage gated Na+ OPEN, Na+ enters the cell
- K+ channels begin to open SLOWLY
- Rapid Na+ depolarizes cell
- Na+channels CLOSE, and SLOWER K+ -OPEN
- K+ moves from the cell into the extracellular fluid
- K+ channels remain open and addition K+ leaves the cell = HYPERPOLARISATION
- Voltage gated K+ CLOSE, some K+ enter through leak channels
- cell returns to resting Ion potential.
Describe the AP of cardiac muscles.
- Rapid depolarisation –> Na+ influx through open FAST Na+ channels ==> FAST Na+ INFLUX
- Transcient K+ channels open and K+ Efflux returns TMP to 0mV
- PLATEAU–> Influx of Ca2+ is electrically balanced by K+ Efflux through delayed rectifier K+ channels ==> SLOW Ca2+ CLOSING
- Repolarisation: Ca2+ Channels close but delayed rectifier of K+ channels remains open and return TMP to -90mV ==> SLOW K+ CLOSING
- Na+, Ca2+ Channels are closed, open K+ rectifier keep TMP stable at -90mV.
Describe how does the eukaryotic NaV Channel work.
The sodium channel has 4 different gating particles (I-IV), because it is formed from a single gene with 4 subunits joined together. The gating particles are charged stretches of protein buried in the membrane within a special protein domain called the “Voltage Sensor”. They move when Em changes.
- 3 gating particles are fast for opening the channel (DI-DIII)
- 1 gating particle (D-IV) is slow and closes the channel!!
The potassium channel has 4 identical gating particles because it is composed of four identical subunits.
