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

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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.




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

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