PubMed 11306655

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Kv1.5 , Slo1

Title: External K(+) relieves the block but not the gating shift caused by Zn(2+) in human Kv1.5 potassium channels.

Authors: S Zhang, D C Kwan, D Fedida, S J Kehl

Journal, date & volume: J. Physiol. (Lond.), 2001 Apr 15 , 532, 349-58

PubMed link:

1. We used the whole-cell recording technique to examine the effect of extracellular Zn(2+) on macroscopic currents due to Kv1.5 channels expressed in the human embryonic kidney cell line HEK293. 2. Fits of a Boltzmann function to tail current amplitudes showed that 1 mM Zn2+ shifted the half-activation voltage from -10.2 +/- 0.4 to 21.1 +/- 0.7 mV and the slope factor increased from 6.8 +/- 0.4 to 9.4 +/- 0.7 mV. The maximum conductance in 1 mM Zn2+ and with 3.5 mM K(+)o was 33 +/- 7 % of the control value. 3. In physiological saline the apparent KD for the Zn(2+) block was 650 +/- 24 M and was voltage independent. A Hill coefficient of 1.0 +/- 0.03 implied that block is mediated by the occupation of a single binding site. 4. Increasing the external concentration of K(+) ([K(+)]o) inhibited the block by Zn(2+). Estimates of the apparent K(D) of the Zn(2+) block in 0, 5 and 135 mM K(+) were 69, 650 and 2100 M, respectively. External Cs(+) relieved the Zn(2+) block but was less effective than K(+). Changing [K(+)]o did not affect the Zn(2+)-induced gating shift. 5. A model of allosteric inhibition fitted to the relationship between the block by Zn(2+) and the block relief by external K(+) gave KD estimates of approximately 70 M for Zn(2+) and approximately 500 M for K(+). 6. We propose that the gating shift and the block caused by Zn(2+) are mediated by two distinct sites and that the blocking site is located in the external mouth of the pore.