Neuronal P2X transmitter-gated cation channels change their ion selectivity in seconds.
Fast synaptic transmission depends on the selective ionic permeability of transmitter-gated ion channels. Here we show changes in the ion selectivity of neuronal P2X transmitter-gated cation channels as a function of time (on the order of seconds) and previous ATP exposure. Heterologously expressed P2X2, P2X2/P2X3 and P2X4 channels as well as native neuronal P2X channels possess various combinations of mono- or biphasic responses and permeability changes, measured by NMDG+ and fluorescent dye. Furthermore, in P2X4 receptors, this ability to alter ion selectivity can be increased or decreased by altering an amino-acid residue thought to line the ion permeation pathway, identifying a region that governs this activity-dependent change.
Khakh
B S
BS
Division of Biology, California Institute of Technology, Pasadena 91125, USA. balkhakh@its.caltech.edu
Bao
X R
XR
Labarca
C
C
Lester
H A
HA
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D019943:Amino Acid Substitution; D000818:Animals; D001583:Benzoxazoles; D002412:Cations / Q000378:metabolism*; D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000235:genetics; D005456:Fluorescent Dyes / Q000378:metabolism; D017136:Ion Transport; D008536:Meglumine / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011806:Quinolinium Compounds; D051381:Rats; D011978:Receptors, Nicotinic / Q000502:physiology; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D058476:Receptors, Purinergic P2X2; D058477:Receptors, Purinergic P2X3; D058848:Receptors, Purinergic P2X4; D011993:Recombinant Fusion Proteins / Q000502:physiology; D013997:Time Factors
D001583:Benzoxazoles; D002412:Cations; D018076:DNA, Complementary; D005456:Fluorescent Dyes; D009419:Nerve Tissue Proteins; D011806:Quinolinium Compounds; D011978:Receptors, Nicotinic; D018048:Receptors, Purinergic P2; D058476:Receptors, Purinergic P2X2; D058477:Receptors, Purinergic P2X3; D058848:Receptors, Purinergic P2X4; D011993:Recombinant Fusion Proteins; C089813:YO-PRO 1; D008536:Meglumine; D000255:Adenosine Triphosphate