Dual function of Zn2+ on the intrinsic excitability of dopaminergic neurons in rat substantia nigra

J. Noh, S. Y. Chang, S. Y. Wang, J. M. Chung

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13 Scopus citations


Despite the presence of Zn2+ in high levels in Parkinson brain, it is not yet clearly answered whether and how Zn2+ alters the electrical activity of neurons in substantia nigra (SN). Here we show that Zn2+ alters the intrinsic activity of nigral dopamine neurons in dual ways, that is, excitation or inhibition, by modulating the gating properties of a transient A-type K+ (KA) channel. Depending on the holding potential, Zn2+ could reduce or enhance a transient outward K+ current (IA) in nigral dopamine neurons. Zn2+ slowed the kinetics of both IA activation and inactivation with the rate of activation much more reduced than that of inactivation. Zn2+ also increased the rate of release from IA inactivation. Both activation and inactivation IA curves were shifted by Zn2+ towards positive potentials, but the positive shift of the inactivation curve was much greater than that of the activation curve. We propose that all these effects of Zn2+ on KA channel gating properties underlie the dual mode of Zn2+ action on IA, that is, attenuation or potentiation depending on membrane potential. As a result, Zn2+ increased a bursting activity of a nigral dopamine neuron elicited by anodal break excitation presumably through IA reduction at a hyperpolarizing state, whereas Zn2+ decreased its tonic activity at either resting or depolarizing states where IA was increased. This was further supported by the observations that 4-aminopyridine (4-AP), a well-known KA channel blocker, strengthened or counteracted the effect of Zn2+ on the intrinsic excitability of nigral dopamine neurons.

Original languageEnglish
Pages (from-to)85-92
Number of pages8
StatePublished - 17 Feb 2011

Bibliographical note

Funding Information:
We are grateful to Drs. Jaesang Kim and Eun-Kyung Suh for reading the manuscript. This work was supported by the Systems Biology Infrastructure Establishment Grant from GIST and the National Research Foundation Grant from KMEST ( 2010-0008120 ) to JMC; Noh, EWU RP-Grant 2010 recipient.


  • Pacemaker
  • Voltage-gated potassium channel
  • Zinc


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