Lecture 6 - 1 BIO 317 Principles of Cellular Signaling...

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Unformatted text preview: 1 BIO 317 Principles of Cellular Signaling Lecture 6 Correlating Na + Channel Structure and Function • α-subunit: • is composed of about 20,000 amino acid residues with • 4 homologous repeats (I - IV) • each repeat contains 6 transmembrane segments (S1 - S6) • S4 segments contain charged residues and serve as voltage sensor • extracellular loops between S5 & S6 determine ion selectivity • cytosolic link between repeats III & IV plays key role in anactivation From: Ion Channels and Disease by F. Ashcroft 2 Correlating Na + Channel Structure and Function • Tetrodotoxin (TTX) binds to the outer mouth of the Na + channel, plugging the pore. • Therefore, point mutations in Na + channel protein that disrupt TTX action should deFne the outer mouth of the pore • Same approach can be used with local anesthetics to deFne the inner mouth of pore. ¡rom: Ion Channels and Disease by ¡. Ashcroft Na + Channel Inactivation ¡rom: Ion Channels and Disease by ¡. Ashcroft • Cytosolic loop connecting repeats III & IV contain a cluster of three key amino acids hydrophobic residues important for inactivation...
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Lecture 6 - 1 BIO 317 Principles of Cellular Signaling...

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