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.
Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.