Zn2+ modulation of neuronal transient K+ current: Fast and selective binding to the deactivated channels

17Citations
Citations of this article
8Readers
Mendeley users who have this article in their library.

Abstract

Modulation of voltage-dependent transient K+ currents (A type K+ or K(A) current) by Zn2+ was studied in rat hippocampal neurons by the whole- cell patch-clamp technique. It is found that Zn2+ selectively binds to the resting (deactivated or closed) K(A) channels with a dissociation constant (K(d)) of ~3 μM, whereas the affinity between Zn2+ and the inactivated K(A) channels is 1000-fold lower. Zn2+ therefore produces a concentration- dependent shift of the K(A) channel inactivation curve and enhances the K(A) current elicited from relatively positive holding potentials. It is also found that the kinetics of Zn2+ action are fast enough to compete with the transition rates between different gating states of the channel. The rapid and selective binding of Zn2+ to the closed K(A) channels keeps the channel in the closed state and explains the ion's concentration-dependent slowing effect on the activation of K(A) current. This in turn accounts for the inhibitory effect of Zn2+ on the K(A) current elicited from hyperpolarized holding potentials. Because the molecular mechanisms underlying these gating changes are kinetic interactions between the binding-unbinding of Zn2+ and the intrinsic gating processes of the channel, the shift of the inactivation curve and slowing of K(A) channel activation are quantitatively correlated with ambient Zn2+ over a wide concentration range without 'saturation'; i.e.. The effects are already manifest in micromolar Zn2+, yet are not saturated even in millimolar Zn2+. Because the physiological concentration of Zn2+ could vary over a similarly wide range according to neural activities, Zn2+ may be a faithful physiological 'fine tuner,' controlling and controlled by neural activities through its effect on the K(A) current.

Cite

CITATION STYLE

APA

Kuo, C. C., & Chen, F. P. (1999). Zn2+ modulation of neuronal transient K+ current: Fast and selective binding to the deactivated channels. Biophysical Journal, 77(5), 2552–2562. https://doi.org/10.1016/S0006-3495(99)77090-6

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free