Aromatic residues affecting permeation and gating in dSlo BK channels |
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| Authors: | Armando A Lagrutta Ke-Zhong Shen André Rivard R Alan North J P Adelman |
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| Institution: | (1) Vollum Institute, Oregon Health Sciences University, 3181 SW Sam Jackson Park Rd., Portland, OR 97201, USA, US;(2) Department of Pharmacology, Merck Research Laboratories, PO Box 4, WP46-300, West Point, PA 19486-0004, USA, US;(3) Physiology and Pharmacology Department, Oregon Health Sciences University, 3181 SW Sam Jackson Park Rd., Portland, OR 97201, USA, US;(4) Glaxo Institute for Molecular Biology, 14 Chemin des Aulx, 1228 Plan-Les-Oautes, Geneva, Switzerland, CH |
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| Abstract: | Structural determinants of permeation in large unit conductance calcium-activated potassium channels (BK channels) were investigated.
Y293 and F294 in the P-region of dSlo were substituted by tryptophans. Compared to wild-type channels, Y293W channels displayed reduced inward unitary currents
while F294W channels exhibited normal inward current amplitudes but flickery kinetics. Both mutations produced changes in
current/voltage relations under bi-ionic conditions. Sensitivity to block by external tetraethylammonium (TEA) was affected
in both channels, and the voltage dependence of TEA block was increased in F294W channels. Both mutations also affected gating
by shifting the half-maximal activation voltage of macroscopic conductance/voltage relations to more positive potentials,
and eliminating a slow component of deactivation. The double mutant did not produce ionic currents. These data are consistent
with a model in which Y293 contributes to a potassium-binding site close to the outer mouth of the dSlo pore, while F294 contributes to an energy barrier near this site.
Received: 16 September 1997 / Received after revision: 20 November 1997 / Accepted: 21 November 1997 |
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| Keywords: | Pore region P-loop K+ channel Ca2+-activated K+ channels Site-directed mutagenesis |
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