title: Dual function of Zn2+ on the intrinsic excitability of dopaminergic neurons in rat substantia nigra.
abstract: Despite the presence of Zn(2+) in high levels in Parkinson brain, it is not yet clearly answered whether and how Zn(2+) alters the electrical activity of neurons in substantia nigra (SN). Here we show that Zn(2+) 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(+) (K(A)) channel. Depending on the holding potential, Zn(2+) could reduce or enhance a transient outward K(+) current (I(A)) in nigral dopamine neurons. Zn(2+) slowed the kinetics of both I(A) activation and inactivation with the rate of activation much more reduced than that of inactivation. Zn(2+) also increased the rate of release from I(A) inactivation. Both activation and inactivation I(A) curves were shifted by Zn(2+) 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 Zn(2+) on K(A) channel gating properties underlie the dual mode of Zn(2+) action on I(A), that is, attenuation or potentiation depending on membrane potential. As a result, Zn(2+) increased a bursting activity of a nigral dopamine neuron elicited by anodal break excitation presumably through I(A) reduction at a hyperpolarizing state, whereas Zn(2+) decreased its tonic activity at either resting or depolarizing states where I(A) was increased. This was further supported by the observations that 4-aminopyridine (4-AP), a well-known K(A) channel blocker, strengthened or counteracted the effect of Zn(2+) on the intrinsic excitability of nigral dopamine neurons.
authors.affiliation: Department of Brain and Cognitive Sciences and Brain Disease ResearchInstitute, Ewha Womans University, Daehyun-dong, Seodaemun-Gu, Seoul 120-750, Korea.
authors.forename: J
authors.initials: J
authors.lastname: Noh
authors.forename: S Y
authors.initials: SY
authors.lastname: Chang
authors.forename: S Y
authors.initials: SY
authors.lastname: Wang
authors.forename: J M
authors.initials: JM
authors.lastname: Chung
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D002413:Cations, Divalent / Q000494:pharmacology; D002478:Cells, Cultured; D059290:Dopaminergic Neurons / Q000378:metabolism / Q000502:physiology*; D015640:Ion Channel Gating / Q000502:physiology; D008564:Membrane Potentials / Q000502:physiology; D009433:Neural Inhibition / Q000502:physiology; D009924:Organ Culture Techniques; D015221:Potassium Channels / Q000145:classification / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D015032:Zinc / Q000502:physiology*
chemical_list: D002413:Cations, Divalent; D015221:Potassium Channels; D015032:Zinc