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Channels
- V-G
- Ligand-g: extracellular; intracellular
- Stretch- and Heat activated
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VG channels
- highly selective
- how K channels so selective- allow 1 Na for every Na? b/c energetically fav to K and carobnyl oxygens
- -tetramer (K) or pseudotetramer (Na&Ca)
- -6 transmembrane spaing segments
- -P region- between 5 & 6, affect permeation (ion sensitivity, block by drugs/toxins)
- -Voltage sensor: alt sew of hydrophob & basic POSITIVE aa; ever 3rd i slysine or arginine
- -"ball and chain"
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VG K
delayed rectifier K channel
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VG Na
Inactivation-> refractory period
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VG Cl-
? inhibitory effect, usually by inc "leakage" g NOT hyperpol cell
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VG Ca
- conversion of elect->chem signal
- vesicle fusion, gen xpression, kinase activation
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use-dependent block
- drug more potent as AP firing is higher.
- higher affin to depol confirmation (slowere unbinding rate)
- binds to inactivated channel and block
- helps with fast arrythmias, specific
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Facts
- Acquired autoimmune responses against channels may accompany cancers.
- Channelopathies affectin excitable tissue-> brain, heart, m, brain
- pt/missense mutations
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3 features of excitable tissue disorders
- 1. autosomal dominant
- 2. episodic attacks
- 3. affect a SINGLE organ- many isoforms, specific for that tissue
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myotonia
- goats with myotonia also
- lower AP
- slower subthresh response
- increased R-> dec g of Cl-
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Cl- channel-based myotnia
- Cl is passive, voltage determines what it does (instead of other way round)
- Cl moven in/out until Nernst pot for Cl = resting pot
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both myotonia & PP
excessive Na current, NOT a Cl g defect
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Na gain of function defect
- persistent Na current (incomplete inact, enhanced activ)
- DEPOLARIZATION->-> in turn inactiv wt and mutant Na channels-> refractory-> flaccid paralysis!!
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