PHYL3001 Lecture Notes - Lecture 5: Inker, Enzyme, Immunosuppression

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LECTURE FIVE: Ion Channel Structure and Function
Voltage-Gated-Like Ion Channel Superfamily:
143 genes that encode for VGL channels
Major branches define groups of related channel genes
o K+ channels largest family, classified based on different
properties
o TRP channels transient receptor potential
o Na+/Ca2+ channels
o CNG and HCN channels cyclic nucleotide gating channels,
hyperpolarizing activated channels
Structure of Voltage-Gated K+ Channels (Kv)
Hydrophobicity peaks correspond to transmembrane segments S1-S6
Conserved structural feature of all voltage gated K+ channels
S1-S4 segments
o S4 voltage sensor domain
o Amino acid sequence of S4 domain is highly conserved in evolution
o Contains +ve charged arginine or lysine residues
S5-P-S6 segments
o P pore domain
o Region contains selectivity filter and binding sites for toxins and
blocking molecules (e.g. TEA)
o Contains amino acid residues critical for K+ selectivity
K+ channels are the largest and most diverse family of voltage-gated ion
channels
Humans have at least 79 distinct genes encoding K+ channels
Kv believed to represent an evolutionary precursor to Nav and Cav
channels because pore-forming subunits contains only 1 S1-S6 domain
Kv channels made up of 4 a subunits and 4 cytoplasmic b subunits
Movement of S4 Segment During Gating:
At rest
o +ve charged arginine residues balanced by neighboring ve charge
Depolarization
o +ve charge moved outward until balanced by ve charge on
adjacent helix stabilizing channel in new conformation
o Screw-type movement causes 4 S6 helices which form inner lining
of pore to bend away from pore axis
o Channel opened
Selectivity Filter:
Pore shaped like an inverted teepee with narrow selectivity filter
Minimizes distance that K+ interacts with the channel
Large water-filled cavity and ve charged helix dipoles help overcome
electrostatic energy barrier in low dielectric membrane center
Selectivity filter lined by carbonyl oxygen atoms
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