Question

Tetrodotoxin and lidocaine are both drugs that cause local analgesia or numbness where applied to the skin.  Explain this outcome, with reference to the effects on membrane potentials, ion flux and overall neuronal activity. Would you predict that these drugs could affect other neurons than just those mediating cutaneous sensation? If so, how? If not, why not?

Answer 1

Tetrodotoxin: In normal neurons, there is high concentrations of K+ ions and low concentrations of Na+ ions in axon. Hence, axons have negative potential. When axons are stimulated by impulses, there is flow of Na+ into the cell via sodium channels, resulting in positive membrane potential. This results in membrane depolarization. When the depolarization reaches a threshold value, action potential results. This stimulates neuronal activity.

Tetrodotoxin is the poison produced majorly by the puffer fish. It is a virulent poison that blocks the conduction of nerve impulses in nociceptors on skin that indicate pain. Tetrodotoxin blocks the Na+ ion channel protein and competes with Na+ ions. Tetrodoxin has higher affinity for the channel than Na+. As a result, there is no flow of Na+ into the cells, thereby creating/retaining a negative potential. This results in prevention of depolarization of the neuronal membrane. As a result, no action potential is generates and neuronal activity is inhibited. This toxin has no effect on K+ ions. Low doses in skin will cause local analgesia and numbness. However, high does may result in respiratory paralysis.

Lidocaine: Lidocaine blocks sodium channels, thereby inhibiting action potential in vasoconstrictor sympathetic nerves. Blocking of sodium channels will inhibit the influx of sodium in response of nerve impulses. As a result, the membrane potential remains negative and there is no depolarization. This results in absence of action potential and inhibition of neuronal activity. There is vasodilation induced in response to lidocaine. As a result, there is local analgesia and numbness, causing local anaesthesia.

Both lidocaine and tetrodotoxin cause local analgesia and numbness in skin when applied. This action is linked to inhibition of sodium channels. Lidocaine is known to be neurotoxic while tetradotoxin is not. When these inhibitors are added at low concentration, they will affect only pain reception and cause numbness. However, at high concentration, the inhibition of nerve signals to other neurons will be affected as the effect is prolonged. The other neurons will not be able to respond due to failure of signal transmission from the sensory receptors/vasoconstrictor sympathetic neurons. As a result, the can be effects on respiratory system, causing respiratory distress. This is due to reduction/inhibition of muscle contraction.