Molecular studies of the asymmetric pore structure of the human cardiac voltage-dependent Ca2+ channel. Conserved residue, Glu-1086, regulates proton-dependent ion permeation

Udo Klöckner, G. Mikala, Arnold Schwartz, Gyula Varadi

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Proton transfer to calcium channels results in rapid fluctuations between two non-zero conductance levels when the current is carried by monovalent cations. A combination of site-directed mutagenesis and single- channel recording techniques were used to identify the unique proton acceptor site as Glu-1086, a conserved glutamate residue located in the S5-S6 linker of motif III of calcium channels. Glu-1086 is part of an array of four glutamate residues in the pore-lining region of the channel conferring the high selectivity of calcium channels. Titration of Glu-1086 yielded a pK(α) value of 7.91 which is different from that expected for a free glutamic acid side-chain carboxyl. Proposed electrostatic interactions between charged nearby residues can account only in part for this phenomenon since individual elimination of the other three glutamate residues only slightly decreased the pK(α) of Glu-1086. These data, in addition to identifying the proton accepter site, provide evidence for the influence of the microenvironment in forming the asymmetry of the conducting pathway of calcium channels.

Original languageEnglish
Pages (from-to)22293-22296
Number of pages4
JournalJournal of Biological Chemistry
Volume271
Issue number37
DOIs
Publication statusPublished - 1996

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Calcium Channels
Pore structure
Permeation
Protons
Glutamic Acid
Ions
Electric potential
S 6
Monovalent Cations
Mutagenesis
Proton transfer
Site-Directed Mutagenesis
Coulomb interactions
Static Electricity
Titration
Linings

ASJC Scopus subject areas

  • Biochemistry

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Molecular studies of the asymmetric pore structure of the human cardiac voltage-dependent Ca2+ channel. Conserved residue, Glu-1086, regulates proton-dependent ion permeation. / Klöckner, Udo; Mikala, G.; Schwartz, Arnold; Varadi, Gyula.

In: Journal of Biological Chemistry, Vol. 271, No. 37, 1996, p. 22293-22296.

Research output: Contribution to journalArticle

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