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

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

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 (US)
Pages (from-to)85-92
Number of pages8
JournalNeuroscience
Volume175
DOIs
StatePublished - Feb 17 2011

Keywords

  • Pacemaker
  • Voltage-gated potassium channel
  • Zinc

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Dual function of Zn<sup>2+</sup> on the intrinsic excitability of dopaminergic neurons in rat substantia nigra'. Together they form a unique fingerprint.

  • Cite this