I know that the concepts within this lecture can seem intimidating and difficult. Challenge yourself to sit with it a bit and see if you can reduce what was discussed over a two-hour period into 3-4 main points of the lecture. In essence, there was actually not that much 'material' covered, just a difficult concept. If you have no idea where to start, start with some practice questions. CTL has posted questions on this topic and pick 1-4 of those on Neurophysiology and work through them. See if you can do three things with each question:
1. Determine what the right answer is, and why (the why is more important).
2. Determine why all of the other answers are incorrect.
3. Re-write either the question or the answer choices to make each of them correct.
This strategy will allow you to study everything surrounding an individual topic and determine what areas of the lecture you are still struggling with. Those areas you can then go back and study or create questions around to get answers.
Here are the questions I have from your classmates thus-far. As always, if there are others please feel free to leave them in a comment (anonymously is completely fine!) or send me an email.
1) On slide 26 you have written out the Goldman-Hodgkin-Katz Voltage equation on the slide and in your notes, but the Cl is in the correct spot only in your notes. (I mean that the Cl is supposed to be inverted because it's negative, but the slide has it looking like all the other ions).
I do understand that the equation is written differently on the slide and in the notes. Remember that on the slide there is a negative sign out front and therefore the concentrations for Cl- are outside/inside, whereas the equation in the notes does NOT have a negative sign out front and therefore the concentrations for Cl- are inside/outside. This would allow you to deal with the negative charge of Cl- in that manner rather than simply putting it out front of the equation.
2) On slide 28 you say "Without this pump, the gradual leak of K+ out of the cell and Na+ into the cell would slowly dissipate the ionic gradients, resulting in a membrane potential of zero." How is the Na getting into the cell without a pump, I thought only K had a leak channel that it could passively diffuse through?
Although there are not direct leak channels for Na+, there can be some Na+ that moves through facilitated transporters and some through voltage-gated channels that may be open incorrectly at that voltage. Therefore, it is certainly not MUCH, but as the membrane becomes depolarized (with the increase in extracellular K+), the voltage-gated Na+ channels would open allowing for the movement of Na+ into the cell.
In the notes of slide 28 I am also confused about the difference between how the pump directly and indirectly contributes to the Vm.
Vm (the membrane potential) is the difference in charges that occurs across an excitable cell (as indicated in the next question). Vm is constantly changing slightly due to the opening and closing of voltage-gated and ligand-gated ion channels allowing for ions to flow across the membrane. However, the resting membrane potential (also indicated by Vm) is maintained by the Na/K pump as it brings K+ and Na+ ions back to where they belong allowing for their flow down their electrochemical gradient to continue to occur. In this way, therefore, Vm is maintained directly by the Na/K pump, but not created by the pump. You could argue, and the above statement does argue, that this movement of Na/K is also helping establish this negative Vm, and indeed it does to a slight extent and is defined, therefore, as an indirect creation of Vm.
3) Can you clarify for me what the difference is between membrane potential and resting membrane potential.
These two terms are frequently used interchangeably. However, by definition the resting membrane potential is the membrane potential where a given excitable cell reaches at the end of the action potential and where the membrane potential will reside if no excitable communication is occurring (between action potentials). However, that moment is only a moment and therefore does not last. By definition, a membrane potential is a difference in charges across a membrane and this difference in charges is quite fluid. In physiological circumstances, ions are continuously moving from one side of the membrane to the other and the membrane potential is continuously changing (as you will see on Monday).
4) How does a decrease in K permeability cause the membrane potential to be less negative than the resting membrane potential. I understand that if the extracellular K goes up then there is less of a gradient and therefore the membrane potential will be less negative, but how does blocking K channels cause extracellular K to increase?
Blocking K+ channels will not cause the extracellular K+ concentration to increase. I am unsure of where you saw this stated. A decrease in K+ permeability through the Na/K pump, on the other hand is a different story. Blocking the Na/K Pump would reduce the movement of K+ from ECF back to the ICF, thereby allowing for K+ ions to move through the leak channels from the ICF to the ECF (down its electrochemical gradient) and not bring them back. This would cause the extracellular K+ concentration to increase, causing the equilibrium potential for K+ to depolarize (also causing the gradient to decrease), thereby causing the resting membrane potential to also depolarize (as it is dependent mostly on the equilibrium potential for K+).
5) Regarding Question #8 of the Thought Problems, can you help explain how we can calculate and understand what the RMP would be?
Question 8 gives a variety of scenarios where you have a system with ECF and ICF ionic concentrations. For each system you will have equilibrium potentials for all ions within the system. The resting membrane potential, however, will only depend upon the ions that the membrane is permeable to. Therefore, you can utilize the Goldman-Hodgkin-Katz equation to calculate out a membrane potential if there are multiple ions the membrane is permeable to, or you can use the Nernst Equation to calculate the membrane potential if the membrane is only permeable to a single ion.
6) I was going through the thought problems on slide 24 of today's
lecture and got confused with the thought problems:
Thought Problem 1: The instant membrane potential is +10 mV when a potassium channel opens. Will potassium influx or efflux? What would be the driving force?
Thought Problem 2: The instant membrane potential is
-40 mV when a sodium channel opens. Will sodium influx or
efflux? What would be the driving force?
Is the instant membrane potential what you want the intracellular
potential to be? And is it assumed that we will start from a resting membrane
potential of -70 mV? Wouldn't there be an influx in both cases since you want
to get to a more positive membrane potential?
These thought problems are designed to ask you to determine what way would an ion move if the membrane potential were at a given point (instant membrane potential) and you made the cell permeable to the given ion (K+ or Na+). The one thing you do need to assume, however, is the typical equilibrium potential for K+ and Na+ (-90 mV and +60 mV respectively). Therefore, from +10 mV, which direction would K+ move to bring the membrane to -90 mV, and what would be the driving force (remember that driving force = Vm-Ex). The same is true for the second question except it is saying from -40 mV, what direction would sodium move to bring the membrane to its equilibrium potential of +60 mV, what would be the driving force?
7) Regarding the following question provided by CTL: 24. Solutions A and B are separated by a semi-permeable
membrane that is permeable to Ca2+ and impermeable to Cl-. Solution A contains 10 mM CaCl2, and solution
B contains 1 mM CaCl2. At physiological
temperatures, Ca2+ will be at electrochemical equilibrium when which of the
following is achieved?
A. Solution A is +60 mV
B. Solution A is +30 mV
C. Solution A is -60 mV
D. Solution A is -30 mV
E. Solution A is +120 mV
F. Solution A is -120 mV
G. The Ca2+ concentrations of the two solutions are equal
H. The Cl- concentrations of the two solutions are equal
I think I have to use the Nerst Equation but I don't know
how.
Indeed you DO need to use the Nernst equation for this question. There are two separate ways, however, that this can be achieved. The most basic way would be to just plug in numbers (10mM and 1mM) and calculate out what the difference in voltage across the membrane is. If you do that, you discover that there is a 30mV difference across the membrane. From there you would like to determine which side would have a particular charge. Since all of the answer choices reference solution A, you need to determine what is the charge of solution A. If the membrane is made permeable to Ca2+, then Ca2+ will move down its concentration gradient from solution A (where there is higher concentration) to solution B. This will bring Ca2+ to solution B causing solution B to be positively charged and solution A to be negatively charged. Therefore, solution A will be -30 mV.
Alternatively, you could utilize the Nernst equation directly. The equation is written to calculate the concentration on the outside of the cell with respect to the inside to determine the membrane potential of the inside of the cell with respect to the outside. Therefore, since all of the answer choices are solution A (with respect to solution B), therefore Solution A becomes the intracellular and solution B becomes the extracellular. Then, utilizing the equation directly you can put 10 mM in for the concentration of intracellular solution and 1 mM for the concentration of the extracellular solution. If you do that, you get -30mV of Solution A.
8) Regarding the following question provided by CTL: 20. A cell has the
following membrane conductances: gk = 1
nS; gNa = 0.02 nS; gCl = 0.01 nS, and intracellular and extracellular solutions
are given below. Exposure to a bee venom
toxin poisons all potassium channels in the cell so that they can no longer
open. As a result, what will happen to
Vm?
Chord-conductance equation: Vm = gk/gtot(EK) +
gNa/gtot(ENa) + gCl/gtot(ECl)
Extracellular Intracellular
146 mM Na+
6 mM Na+
4 mM K+ 144 mM K+
150 mM Cl- 12 mM Cl-
138 mM
gluconate anion
How would I start this? I am confused.
You can attack this question in two approaches as well. The Chord-Conductance equation is given, as are the concentrations of the given ions. Therefore, you could calculate the equilibrium potentials for Na+, K+, and Cl- and determine the Vm given the conductances. Then you could remove the conductance for K+ from the equation (as the question indicates), and re-calculate Vm. This would allow you to answer the question.
Alternatively, you could look at this conceptually. If you calculate out the equilibrium potentials (using the Nernst Equation) for the three ions, you know that the membrane potential is closest to the equilibrium potential for K+ (because it has the greatest conductance or permeability). If, however, you then remove the conductance for K+ by exposure to the bee venom toxin, the effect of K+ on the membrane potential is removed. Therefore, the membrane potential is solely dependent on the equilibrium potential for Na+ and Cl- (twice as much on Na+ than Cl-), and the membrane potential would then become closer to the Na+ equilibrium potential.
