Snapshot A 24-year-old patient presents with rapid onset dizziness, nausea, and weakness at a restaurant in Japan. Prior to this presentation, it was disclosed to the paramedics that he had been eating a Japanese delicacy. (Tetrodotoxin poisoining from consumption of pufferfish) Overview Action Potential Action potential resting membrane potential (-70 mV) determined by permeability to potassium (K+), sodium (Na+), and chloride (Cl-) roughly -70 mV, with the greatest permeability being to K+ threshold (approximately -55 mV) neuron must receive enough stimulus to reach threshold depolarization is all or nothing if threshold is met the neuron depolarizes if it is not met nothing happens depolarization (+50 mV) once threshold is met, voltage-gated Na+ channels open Na+ rushes into the cell (there is a high electrochemical gradient for Na+ to enter) this creates a short term positive feedback loop where the increasing voltage opens more voltage-gated Na+ channels membrane potential becomes more positive and reaches a value of roughly +50 mV as the membrane reaches its peak voltage, the voltage-gated Na+ channels begin to inactivate spontaneously and rapidly, and voltage gated K+ channels begin to open faster inactivation of sodium channels will lead to lower amplitude of depolarization pathophysiology correlate tetrodotoxin (pufferfish consumption) binds fast voltage-gated Na+ channels in nerve tissue, which does not allow for depolarization or action potential formation can result in nausea, weakness, dizziness or can be fatal treatment is supportive hyperpolarization at the peak membrane voltage (+50 mV), voltage-gated Na+ channels close and delayed outward-rectifier K+ channels open Na+ no longer enters the cell and K+ leaves the cell at a rate greater than baseline the cell hyperpolarizes at a voltage more negative than its baseline (-80 to -90 mV) due to the increased outward K+ flow baseline eventually the K+ channels return to their baseline state and the membrane potential reaches -70 mV again until another stimulus surpasses threshhold NOTE: the ion gradients are continually reestablished by the activity of the Na+/K+ ATPase which pumps 3 Na+ out of the cell for every 2 K+ transported in