Aromatic residues affecting permeation and gating in dSlo BK channels

Armando A. Lagrutta, Ke Zhong Shen, André Rivard, R. Alan North, John P. Adelman

Research output: Contribution to journalArticle

7 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)731-739
Number of pages9
JournalPflugers Archiv European Journal of Physiology
Volume435
Issue number5
DOIs
StatePublished - Mar 18 1998

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Keywords

  • Ca-activated K channels
  • K channel
  • P-loop
  • Pore region
  • Site-directed mutagenesis

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)

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