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S O D I U M A N D S O D I U M C H A N N E L S

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  1. S O D I U M A N D S O D I U M C H A N N E L S

  2. S o d i u m a n d S o d i u m C h a n n e l s FUGU • It’s the only delicacy forbidden to be served • to the Emperor of Japanese • One of few fish that can close their eyes • Genome sequenced

  3. S o d i u m a n d S o d i u m C h a n n e l s CLINICAL SYMPTOMS First stage: Lip and tongue numbness and tingling (paresthesias) Facial and extremity paresthesias Second stage: Rapidly ascending paralysis Nausea and vomiting Final stage: Cardiac dysfunction, CNS dysfunction, and ultimately respiratory failure TREATMENT None – no drug that will reverse the effects of tetrodotoxin poisoning Supportive ABCs Intubate, IVs to support circulatory collapse, gastric lavage with charcoal OUTCOME 50-60% mortality (those who survive do so without any side effects)

  4. S o d i u m a n d S o d i u m C h a n n e l s TETRODOTOXIN Produced by bacteria: Pseudoalteromonas haloplanktis tetradonis Concentrated in the liver, gonads, and skin spines of the fugu through the action of a specific binding protein Muscle is free of toxin and can be eaten Toxin is thermo-stable

  5. S o d i u m a n d S o d i u m C h a n n e l s TETRODOTOXIN All the clinical effects result from blockade of the voltage gated Na+ channel Can not cross the Blood-Brain-Barrier Affects the brain through a break in the BBB: the area postrema Neurons directly in the vicinity of the area postrema are responsible for respiratory control, cardiovascular tone, consciousness

  6. S o d i u m a n d S o d i u m C h a n n e l s tetrodotoxin Why don’t the puffer fishdye from their own toxin?

  7. S o d i u m a n d S o d i u m C h a n n e l s SODIUM HOMEOSTASIS Complex - controlled primarily by the kidneys and the CNS Normal conc. = 135 – 145 mM Things can wrong and Na+ conc. can drop well below normal levels (vomiting) or rise well above the normal conc. (dehydration) Goal is to normalize serum Na+

  8. S o d i u m a n d S o d i u m C h a n n e l s PSYCHOGENIC POLYDIPSIA Non-physiologic need to drink  hyponatremia Serum Na+< 120 mM Goal is to normalize serum Na+

  9. S o d i u m a n d S o d i u m C h a n n e l s CENTRAL PONTINE MYELINOLYSIS Normal Sagital MRI

  10. S o d i u m a n d S o d i u m C h a n n e l s