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Inhibition of ATP‐activated current by zinc in dorsal root ganglion neurones of bullfrog
Author(s) -
Li Chaoying,
Peoples Robert W.,
Weight Forrest F.
Publication year - 1997
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.1469-7793.1997.641ba.x
Subject(s) - bullfrog , chemistry , biophysics , adenosine triphosphate , reversal potential , patch clamp , dithiothreitol , membrane potential , dorsal root ganglion , biochemistry , endocrinology , anatomy , biology , dorsum , enzyme , receptor
1 The effect of Zn 2+ on ATP‐activated current was studied in bullfrog dorsal root ganglion (DRG) neurones using the whole‐cell patch‐clamp technique. 2 Zn 2+ (2–800 μ m ) inhibited current activated by submaximal concentrations of ATP. The Zn 2+ concentration that produced 50% inhibition (IC 50 ) of current activated by 2.5 μ m ATP was 61 ± 9.8 μ m . When ATP concentrations were adjusted to account for chelation of Zn 2+ , the IC 50 of Zn 2+ was 86 ± 18 μ m . 3 The inhibitory action of Zn 2+ on ATP‐gated channels did not appear to be due to a decrease in the concentration of one or more species of ATP. 4 Zn 2+ inhibition of ATP‐activated current was independent of membrane potential between −80 and +40 mV, and did not involve a shift in the reversal potential of the current. 5 Zn 2+ (100 μ m ) shifted the ATP concentration‐response curve to the right in a parallel manner, increasing the EC 50 for ATP from 2.5 ± 0.5 μ m to 5.5 ± 0.4 μ m . 6 Zn 2+ decreased the time constant of deactivation of ATP‐gated ion channels without affecting the time constant of activation or desensitization. 7 Dithiothreitol (DTT) reversed Zn 2+ inhibition of ATP‐activated current. 8 2‐Methylthio ATP, α,β‐methylene ATP and ADP activated current with EC 50 values of 2.4 ± 0.3, 50.1 ± 5.8 and 303.1 ± 53.9 μ m , respectively. Adenosine, AMP or β,γ‐methylene ATP did not evoke detectable current. 9 Reactive Blue 2 and pyridoxal‐phosphate‐6‐azophenyl‐2′,4′‐disulphonic acid inhibited ATP‐activated current. 10 The results suggest that Zn 2+ can inhibit P2X purinoceptor function by decreasing the affinity of the binding site for ATP. These observations provide the first evidence for this action of Zn 2+ on a neurotransmitter‐gated ion channel. Furthermore, the receptor‐channel in these neurones appears to be a novel member of the P2X purinoceptor class.