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UseCase7 tetrodotoxin
Example of selective blocking of ion transporters
Tetrodotoxin, a neurotoxin, specifically blocks Na+ transport channels. The chemical is found in puffer fish which have accumulated a bacteria. The fish possess an immunity due to a mutation in a component protein of their Na+ channels. -{Boelsterli 2003}-. Terodotoxin(TTX) is a bulky hydrophillic compound containing a cationic group and a guanidine moiety.
Tetrodotoxin binds, one-to-one reversible, to SS2 region of the sodium channel II physically blocking the outside channel from allowing sodium flux into the cell. Upon entering the channel, terodotoxin blocks the outer channel regardless of whether it is open or closed -{Bosteli 2007}-. Inhibition occurs in a 1:1 relationship through a hemilactal bond with the Na+ channel and carbon-10 of tetrodotoxin -{Hille 1975}-. The toxin blocks fast current sodium channels and therefore does not affect cardiac pacemaker cells. However, the cardiac myocetes surrounding the cardiac pacemaker cells do express the fast current Na+ channels and inhibition results in cardiac arrest.
Representational
Biochemical Cell type specification Chemical derivatives Specification of protein domain Organ specific effects Expression(language requirements) Biological dispositions Relative spatial location and orientation Functional (Question and Answers) Q. “Which mechanism involves inhibition of sodium channels?” A.“The mechanism of selective blockage of Voltage Gated Na+ channels by tetrodotoxin” Query:‘mechanistic toxicology process specification’ that ‘has part’ some ‘inhibition of sodium channel’ Q.“What type of sodium channels are involved?” A.“Sodium channel type II” Query: ‘sodium channel’ that ‘is part of some’ (‘molecular complex’ that ‘is agent in’ some ‘inhibition of sodium channel’) *not tested Q.“What domain of the sodium channel type II does tetrodotoxin bind?” A.“The SS2 region” Query: Q.“Where is the bound tetrodotoxin on the sodium channel type II?” A.“The outer channel” Query:Thing that ‘is part of’ some ‘sodium channel type II and ’is location of’ some ‘tetrodoxin’ *not tested Q.“What are the results of this mechanism?” A. “cardiac arrhythmia, cardiac arrest, muscle paralysis” Query: disease that ‘is result of’ some (process that ‘is part of’ some ‘mechanism of selective blockage of voltage gated Na+ channels by tetrodotoxin’) *not tested Q. “What process is causes muscle paralysis by tetrodotoxin?” A.“inhibition of” Query:process that realizes some (‘to cause muscle paralysis’ that ‘is disposition of’ some tetrodotoxin) *not tested Q. “Where does this process occur?” A.“Peripheral nervous system” Query:Thing that ‘is location of’ some (process that realizes some (‘to cause muscle paralysis’ that ‘is disposition of’ some tetrodotoxin)) *not tested
1. Tetrodotoxin binding to sodium channel 2. Blocking sodium channel and inhibiting function resulting in inhibition of action potential in skeletal neurons. 3. Results in muscle paralysis in skeletal tissue. ‘SS2 region’ subClassOf ‘amino acid sequence’ that ‘is part of’ some ‘sodium channel type II’ ‘tetrodotoxin sodium channel II complex formation’ subClassOf ‘molecular complex formation’ that ‘has target’ some tetrodotoxin’ that ‘has target’ some (‘SS2 region’ that ‘is part of’ some ‘sodium channel type II’) and ‘has product’ some ‘tetrodotoxin sodium channel type II complex’ ‘tetrodotoxin sodium channel II complex’ subClassOf ‘molecular complex’ that ‘has proper part’ some ‘tetrodotoxin’ that ‘has proper part’ some ‘sodium channel II’ and ‘has proper part’ some ( ‘outer channel of sodium channel type II’ that ‘is part of’ some ‘sodium channel type II’ and ‘contains’ some tetrodotoxin)) ‘sodium channel type II’ subClassOf ‘sodium channel’ that ‘is part of’ some ‘tetrodotoxin sodium channel II complex’ ‘inhibition of sodium channel II by tetrodotoxin’ subClassOf ‘inhibition of sodium channel II’ that ‘has agent’ some ‘tetrodotoxin sodium channel II complex’ and ‘results in’ some ‘decreased sodium influx via sodium channel type II’ and realizes some (‘to block action potential’ that ‘is disposition of’ some (tetrodotoxin that ‘is part of’ some ‘tetrodotoxin sodium channel II complex’)) and realizes some (‘to inhibit ion transport’ that ‘is disposition of’ some (tetrodotoxin that ‘is part of’ some ‘tetrodotoxin sodium channel II complex’)) ‘sodium influx via sodium channel type II’ subClassOf ‘chemical transport’ that ‘has proper part’ some (‘process start’ and ‘has participant’ some ‘sodium ion’ and ‘is located in’ some ‘extracellular space’) and precedes some (‘chemical transport’ that ‘has agent’ some ‘sodium channel type II’ and ‘is located in’ some ‘plasma membrane’) and precedes some (‘process end’ and ‘has participant’ some ‘sodium ion’ and ‘is located in’ some ‘intracellular space’) ‘decreased sodium influx via sodium channel type II’ subClassOf ‘sodium influx via sodium channel type II’ and ‘results in’ some ‘disruption of action potential’ and ‘has quality’ some (‘process rate’ that ‘is less than relative to’ some (‘process rate’ that ‘is quality of’ some sodium influx via sodium channel type II’)) ‘inhibition of sodium channel II in cardiac mycetes in atrium by tetrodotoxin’ subClassOf ‘inhibition of sodium channel II’ and ‘is located in’ some ‘cardiac tissue’ and ‘results in’ some ‘cardiac arrest’ and ‘results in’ some ‘cardiac arrhythmia’ and realizes some (‘to cause cardiac arrest’ that ‘is disposition of’ some ‘tetrodotoxin’ and ‘in relation to’ some ‘inhibition of sodium channel II in cardiac mycetes in atrium by tetrodotoxin’) and realizes some (‘to cause cardiac arrthymia’ that ‘is disposition of’ some ‘tetrodotoxin’ and ‘in relation to’ some ‘inhibition of sodium channel II in cardiac mycetes in atrium by tetrodotoxin’) ‘inhibition of sodium channel II in peripheral nervous system by tetrodotoxin’ subClassOf ‘inhibition of sodium channel II’ and ‘is located in’ some (nerve that ‘is part of’ some ‘peripheral nervous system’) and ‘results in’ some ‘muscle paralysis’ and realizes some (‘to cause muscle paralysis’ that ‘is disposition of’ some ‘tetrodotoxin) ’inhibition of sodium channel II in central nervous system neurons by tetrodotoxin’ subClassOf ‘inhibition of sodium channel II’ ‘blocked action potential’ subClassOf ‘action potential’ ‘cardiac arrhythmia’ subClassOf ‘disease’ that ‘is result of’ some ‘inhibition of sodium channel II in cardiac mycetes in atrium by tetrodotoxin’
'cardiac arrest' subClassOf 'disease'
that ‘is result of’ some ‘inhibition of sodium channel II in cardiac mycetes in atrium by tetrodotoxin’ ‘muscle paralysis’ subClassOf ‘disease’ that ‘is result of’ some ‘inhibition of sodium channel II in peripheral nervous system by tetrodotoxin’ ‘mechanism of selective blockage of voltage gated Na+ channels by tetrodotoxin’ subClassOf ‘mechanistic toxicology process specification’ that ‘has part’ some ‘tetrodotoxin sodium channel II complex formation’ that ‘has part’ some ‘inhibition of sodium channel II’ and ‘has proper part’ some (‘tetrodotoxin sodium channel II complex formation’ and precedes some ‘inhibition of sodium channel II’)
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