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Characterization of a C‐type natriuretic peptide (CNP‐39)‐formed cation‐selective channel from platypus ( Ornithorhynchus anatinus ) venom
Author(s) -
Kourie Joseph I.
Publication year - 1999
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1999.0359p.x
Subject(s) - conductance , chemistry , platypus , lipid bilayer , biophysics , bilayer , ion channel , analytical chemistry (journal) , membrane , biochemistry , biology , chromatography , receptor , physics , zoology , condensed matter physics
1 The lipid bilayer technique is used to characterize the biophysical and pharmacological properties of a novel, fast, cation‐selective channel formed by incorporating platypus ( Ornithorhynchus anatinus ) venom ( Oa V) into lipid membranes. 2 A synthetic C‐type natriuretic peptide Oa CNP‐39, which is identical to that present in platypus venom, mimics the conductance, kinetics, selectivity and pharmacological properties of the Oa V‐formed fast cation‐selective channel. The N‐terminal fragment containing residues 1‐17, i.e. Oa CNP‐39(1‐17), induces the channel activity. 3 The current amplitude of the TEACl‐insensitive fast cation‐selective channel is dependent on cytoplasmic K + , [K + ] cis . The increase in the current amplitude, as a function of increasing [K + ] cis , is non‐linear and can be described by the Michaelis‐Menten equation. At +140 mV, the values of γ max and K S are 63·1 pS and 169 mM, respectively, whereas at 0 mV the values of γ max and K S are 21·1 pS and 307 mM, respectively. γ max and K S are maximal single channel conductance and concentration for half‐maximal γ, respectively. The calculated permeability ratios, P K : P Rb : P Na : P Cs : P Li , were 1:0·76:0·21:0·09:0·03, respectively. 4 The probability of the fast channel being open, P o , increases from 0·15 at 0 mV to 0·75 at +140 mV. In contrast, the channel frequency, F o , decreases from 400 to 180 events per second for voltages between 0 mV and +140. The mean open time, T o , increases as the bilayer is made more positive, between 0 and +140 mV. The mean values of the voltage‐dependent kinetic parameters, P o , F o , T o and mean closed time ( T c ), are independent of [KCl] cis between 50 and 750 mM ( P > 0·05 ). 5 It is proposed that some of the symptoms of envenomation by platypus venom may be caused partly by changes in cellular functions mediated via the Oa CNP‐39‐formed fast cation‐selective channel, which affects signal transduction.