Some local anaesthetics affect nervous impulse transmission by making it more difficult for voltage-gated sodium channels to open. In a human patient treated with these anaesthetics which of the following statements would be true?
A. The threshold potential required to generate an action potential would be lowered.
B. The axon membrane would become more difficult to repolarise.
C. It would become harder to depolarise the neuron.
D. The membrane potential of the neuron at rest would decrease below –90 mV.
E. The sodium/potassium pump may need to work faster to maintain the resting potential.
It would be useful to keep the central concept that has already been detailed in this question: "…making it more difficult for voltage-gated sodium channels to open." Thus, this concept regarding anaesthetics will be used to rationalize the choices below.
As a reminder, what is the role of voltage gated sodium channels in terms of nerve impulse transmission? Once a stimuli depolarizes the membrane enough to reach threshold potential, these channels respond to the change of transmembrane potential by allowing more sodium ions to pass through, which depolarizes the membrane even more. This allows for the propagation of nerve impulse transmission.
With that being said, let’s rationalize the choices given:
Choice A: This is not the correct choice as it is not in line with the central concept that we established earlier. Anaesthetics affect these voltage-gated channels and not the threshold potential. In such a way, regardless of how often the stimulus induces threshold potential (and regardless of how low the threshold potential is), full depolarization cannot be achieved if sodium ions cannot pass through the membrane in the first place. In addition for clarity sake, a lower threshold potential would also mean it would be easier for stimuli to evoke depolarization, which is not an objective of anaesthetics.
Choice B: Repolarization is not relevant to this question since it is potassium channels that mediate this and not sodium channels. During repolarization, sodium channels close and potassium channels open.
Choice C: This is the correct choice, since it is consistent with the central concept that we established earlier. Without voltage gated sodium channels, there will be no response to the stimuli reaching threshold potential, regardless of the strength of the stimuli. Without the opening of these sodium channels in the first place, it will be much more difficult to depolarize the neuron.
Choice D: Decreasing the resting membrane potential will make it easier for stimuli to induce depolarization, which is not relevant to the objective of anesthetics (which is to make depolarization HARDER), making this an incorrect consideration.
Choice E: Again, the resting membrane potential is not relevant to this question. The effects of anaesthetics is mainly concerned about the ability of voltage gated sodium channels to respond to stimuli depolarizing the membrane enough to reach threshold potential. In this case, voltage gated sodium channels do not play a role in maintaining resting membrane potential, which makes this an incorrect choice.
Thus, only choice C is the correct choice out of all the other choices.
I don’t understand this part if the anesthetic made the resting membrane potential say -120 mV or -150 mV thus decreasing it from -90 mV , doesn’t that imply that the next time depolarization needs to take place the potential of the stimulus will have to be greater than normal to make up for the larger gap between the resting potential and the firing level?
Edit: which is why we have relative refractory period, where the voltage gated sodium channels could open in theory and transmit a signal but won’t because the stimulus required would have to be stronger than usual. So doesn’t choice D create the same effect to an extent?
Local anesthetics keep the Na+ channels in an inactivated state (arrest-state). They do not affect the threshold, the refractory period or the repolarization phase.
This arrest state is achieved when the medicament enters the cell and reach an equilibrium of ionized and un-ionized form. The ionized form binds to open voltage-gated Na+ channels in a reversible and concentration-dependent manner. This episode increases with the frequency of nerve depolarization (use-dependent or phasic block).
Woah! I kinda figured out at some point where i went wrong, realized that the question explicitly specified the mechanism in which the anaesthetic worked, make it harder for voltage gated na+ channels to open, preventing them from responding to sufficient (up to threshold) stimuli, and following through with full depolarization that only they are capable of achieving. But this is a much better and in depth explanation. I never knew what made the voltage gated channels inactivate, or that anaesthetics put the channels in an inactivated state, but it makes perfect sense because inactivated channels don’t respond to stimuli which is exactly what we want from an anaesthetic. Thank you
if the anesthetic made the resting membrane potential say -120 mV or -150 mV thus decreasing it from -90 mV , doesn’t that imply that the next time depolarization needs to take place the potential of the stimulus will have to be greater than normal to make up for the larger gap between the resting potential and the firing level?