Zn2+ Potentiates ATP-activated Currents in Rat Sympathetic Neurons

Overview

Journal Pflugers Arch

Specialty Physiology

Date 1993 Jul 1

PMID 7692385

Citations 27

Authors

R Cloues

S Jones

D A Brown

Affiliations

Soon will be listed here.

Abstract

The ATP-activated inward current (IATP) in cultured rat superior cervical ganglion neurons and its modulation by extracellular Zn2+ were examined. ATP activated a non-specific cation conductance and caused a transient rise in intracellular Ca2+. The current response was specifically activated by ATP and was blocked by the P2-purinoceptor antagonist, suramin. Low concentrations of extracellular Zn2+ rapidly and reversibly potentiated both IATP and the intracellular Ca2+ rise. The potentiation by 10 microM Zn2+ was dependent on the concentration of agonist; Zn2+ increased the sensitivity of activation without potentiating the maximum response. Higher concentrations of Zn2+ reduced and prolonged the current, consistent with open-channel block. We hypothesize that there exist two sites of action for Zn2+: a positively acting allosteric site that enhances current amplitude and a site, possibly within the pore, that blocks conductance through the channel.

Citing Articles

Copper Increases the Cooperative Gating of Rat P2X2a Receptor Channels.

Leiva-Salcedo E, Riquelme D, Huidobro-Toro J, Coddou C Pharmaceuticals (Basel). 2025; 17(12.

PMID: 39770432 PMC: 11678522. DOI: 10.3390/ph17121590.

Mineral Element Deposition and Gene Expression across Different Tissues of Cherry Valley Ducks.

Song Q, Zhang Y, Bai H, Zhong L, Li X, Zhao W Animals (Basel). 2021; 11(1).

PMID: 33477854 PMC: 7832843. DOI: 10.3390/ani11010238.

The Cellular Prion Protein Prevents Copper-Induced Inhibition of P2X(4) Receptors.

Lorca R, Varela-Nallar L, Inestrosa N, Huidobro-Toro J Int J Alzheimers Dis. 2011; 2011:706576.

PMID: 22114745 PMC: 3202100. DOI: 10.4061/2011/706576.

Structural interpretation of P2X receptor mutagenesis studies on drug action.

Evans R Br J Pharmacol. 2010; 161(5):961-71.

PMID: 20977449 PMC: 2972645. DOI: 10.1111/j.1476-5381.2010.00728.x.

Orthosteric and allosteric binding sites of P2X receptors.

Evans R Eur Biophys J. 2008; 38(3):319-27.

PMID: 18247022 DOI: 10.1007/s00249-008-0275-2.

References

Nakazawa K, Fujimori K, Takanaka A, Inoue K . An ATP-activated conductance in pheochromocytoma cells and its suppression by extracellular calcium. J Physiol. 1990; 428:257-72. PMC: 1181646. DOI: 10.1113/jphysiol.1990.sp018211. View

Hamill O, Marty A, Neher E, Sakmann B, Sigworth F . Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch. 1981; 391(2):85-100. DOI: 10.1007/BF00656997. View

Marrion N, Smart T, Brown D . Membrane currents in adult rat superior cervical ganglia in dissociated tissue culture. Neurosci Lett. 1987; 77(1):55-60. DOI: 10.1016/0304-3940(87)90606-9. View

Celentano J, Gyenes M, Gibbs T, Farb D . Negative modulation of the gamma-aminobutyric acid response by extracellular zinc. Mol Pharmacol. 1991; 40(5):766-73. View

Westbrook G, Mayer M . Micromolar concentrations of Zn2+ antagonize NMDA and GABA responses of hippocampal neurons. Nature. 1987; 328(6131):640-3. DOI: 10.1038/328640a0. View

Bean B, Friel D . ATP-activated channels in excitable cells. Ion Channels. 1990; 2:169-203. DOI: 10.1007/978-1-4615-7305-0_5. View

Howell G, Welch M, Frederickson C . Stimulation-induced uptake and release of zinc in hippocampal slices. Nature. 1984; 308(5961):736-8. DOI: 10.1038/308736a0. View

Smart T . A novel modulatory binding site for zinc on the GABAA receptor complex in cultured rat neurones. J Physiol. 1992; 447:587-625. PMC: 1176054. DOI: 10.1113/jphysiol.1992.sp019020. View

Bean B, Williams C, Ceelen P . ATP-activated channels in rat and bullfrog sensory neurons: current-voltage relation and single-channel behavior. J Neurosci. 1990; 10(1):11-9. PMC: 6570347. View

10.

Clementi E, Scheer H, Raichman M, Meldolesi J . ATP-induced Ca2+ influx is regulated via a pertussis toxin-sensitive mechanism in a PC12 cell clone. Biochem Biophys Res Commun. 1992; 188(3):1184-90. DOI: 10.1016/0006-291x(92)91356-u. View

11.

Robbins J, Trouslard J, Marsh S, Brown D . Kinetic and pharmacological properties of the M-current in rodent neuroblastoma x glioma hybrid cells. J Physiol. 1992; 451:159-85. PMC: 1176156. DOI: 10.1113/jphysiol.1992.sp019159. View

12.

Evans R, Derkach V, Surprenant A . ATP mediates fast synaptic transmission in mammalian neurons. Nature. 1992; 357(6378):503-5. DOI: 10.1038/357503a0. View

13.

Allen T, Burnstock G . The actions of adenosine 5'-triphosphate on guinea-pig intracardiac neurones in culture. Br J Pharmacol. 1990; 100(2):269-76. PMC: 1917406. DOI: 10.1111/j.1476-5381.1990.tb15794.x. View

14.

Burnstock G . Purinergic nerves. Pharmacol Rev. 1972; 24(3):509-81. View

15.

Sim J, Cherubini E . Submicromolar concentrations of zinc irreversibly reduce a calcium-dependent potassium current in rat hippocampal neurons in vitro. Neuroscience. 1990; 36(3):623-9. DOI: 10.1016/0306-4522(90)90005-o. View

16.

Magneson G, Puvathingal J, Ray Jr W . The concentrations of free Mg2+ and free Zn2+ in equine blood plasma. J Biol Chem. 1987; 262(23):11140-8. View

17.

Dvergsten C, Fosmire G, Ollerich D, Sandstead H . Alterations in the postnatal development of the cerebellar cortex due to zinc deficiency. I. Impaired acquisition of granule cells. Brain Res. 1983; 271(2):217-26. DOI: 10.1016/0006-8993(83)90284-6. View

18.

Friedman B, Price J . Fiber systems in the olfactory bulb and cortex: a study in adult and developing rats, using the timm method with the light and electron microscope. J Comp Neurol. 1984; 223(1):88-109. DOI: 10.1002/cne.902230108. View

19.

Wright D . Zinc: effect and interaction with other cations in the cortex of the rat. Brain Res. 1984; 311(2):343-7. DOI: 10.1016/0006-8993(84)90097-0. View

20.

Legendre P, Westbrook G . Noncompetitive inhibition of gamma-aminobutyric acidA channels by Zn. Mol Pharmacol. 1991; 39(3):267-74. View