5. You identify a drug that shifts the voltage dependence of voltage-gated sodiu

Question

5. You identify a drug that shifts the voltage dependence of voltage-gated sodium channels, causing them to open at a higher (less negative) membrane potential than usual. a. (2 pts) What is the primary effect that this drug would have on action potentials? Next, you want to quantitatively compare the voltage dependence of the sodium conductance between control drva dnu neurons and drug-treated neurons. Your experiments yield the results shown in the graph to the right. b. (1 pt) On the graph, label which line corresponds to drug8 treatment and which line corresponds to the control condition Membrane potential (mV) C. (5 pts) How would you perform this experiment? Your answer should describe the experimental method, what conditions you would vary, what variable you would directly measure, and how you would analyze your data in order to obtain the graph shown above.

Explanation / Answer

  In response to an electric current (in this case, an action potential), the activation gates of the channel are opened, which allows the Na+  ions to flow into the neuron through the channels thus causing voltage across the neuronal membrane to increase. Hence depolarization condition occurs as the voltage starts to increase. At the peak of the action potential, when enough amount of Na+ has entered the neuron and the membrane's potential has become high enough, the Na+ channels inactivate themselves by closing their inactivation gates, which causes Na+ flow through the channel to stop and the membrane potential stops rising. The neuron will then repolarize and hyperpolarize itself.

c) It is given in the question that the drug shifts the voltage dependance of the channel and cause them to open at a higher action potetial, i.e the condition where a large amount of Na+ ions will be flowing in through the channel. The tremendous therapeutic potential of voltage-gated sodium channels (Navs) has been the subject of many studies in the past and is of great interest today. For eg. in the disease epilepsy, Numerous studies have shown altered levels of mRNA and protein for certain subunits and subunits.

The experiments can be carried out in mice, by preparing a control group and a test group where the mice are given the desired drug, and the changes in action potential is to be measured. The action potential can be meausured by various techniques like the 1) Voltage clamp- This is a method used to to measure the ion currents through the membranes of excitable cells, such as neurons, while holding the membrane voltage at a set level.A basic voltage clamp will measure the membrane potential, and then change the membrane potential (voltage) to a desired value by adding the necessary current. The electrodes are connected to an amplifier, which measures membrane potential and feeds the signal into a feedback amplifier.

2)The patch clamp technique is a technique in electrophysiology used to study ionic currents in individual isolated living cells, tissue sections, or patches of cell membrane. The technique is especially useful in the study of excitable cells such as neurons, cardiomyocytes, muscle fibers, and pancreatic beta cells.In this technique the voltage across the cell membrane is controlled by the experimenter and the resulting currents are recorded.

The other conditions can be kept the same, only the drug should be administered to the test group, and the action potential variations can be evaluated with any of the techniques described above.

There is a mathematical model called as  Hodgkin–Huxley model, or conductance-based model which describes how action potentials in neurons are initiated and propagated. It is a set of nonlinear differential equations that approximates the electrical characteristics of excitable cells such as neurons and cardiac myocytes, and therefore it is a continuous time model. Using a series of voltage clamp experiments and by varying extracellular sodium concentrations, the action potential can be calculated using the differential equations.

Finally, after obtaining the data from the two experimental groups, a graph can be plotted, where the drug treatment might be showing a higher membrane potential.

Related Questions

Navigate

• Browse (All)
• Browse 5
• Subjects

---

---

Integrity-first tutoring: explanations and feedback only — we do not complete graded work. Learn more.