Molecular localization of ion selectivity sites within the pore of a human L-type cardiac calcium channel

S. Tang, G. Mikala, A. Bahinski, A. Yatani, G. Varadi, A. Schwartz

Research output: Contribution to journalArticle

153 Citations (Scopus)

Abstract

A highly conserved position of negatively charged amino acids is present in the SS2 segments of the S5-S6 linker regions among calcium channels. We report here that replacing Glu residues at this position alters the ion selectivity of the human cardiac calcium channel. Substituting Glu334 in motif I or Glu1086 in motif III with Lys produced mutant calcium channels that permeated sodium ions 10-fold more effectively than barium ions. More conservative changes such as substitution of Glu1086 with Gln or substitution of Glu1387 with Ala also increased sodium permeation through the mutant calcium channels. Sodium currents through the mutant calcium channels could be modulated by dihydropyridines and blocked by external divalent cations. These results suggest that Glu334, Glu1086, and Glu1387 are part of a ring of glutamate residues formed in the pore- lining SS1-SS2 region and are critical in determining ion selectivity and permeability of a human cardiac calcium channel.

Original languageEnglish
Pages (from-to)13026-13029
Number of pages4
JournalJournal of Biological Chemistry
Volume268
Issue number18
Publication statusPublished - 1993

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L-Type Calcium Channels
Calcium Channels
Ions
Sodium
Substitution reactions
Dihydropyridines
S 6
Divalent Cations
Barium
Linings
Permeation
Glutamic Acid
Permeability
Amino Acids

ASJC Scopus subject areas

  • Biochemistry

Cite this

Molecular localization of ion selectivity sites within the pore of a human L-type cardiac calcium channel. / Tang, S.; Mikala, G.; Bahinski, A.; Yatani, A.; Varadi, G.; Schwartz, A.

In: Journal of Biological Chemistry, Vol. 268, No. 18, 1993, p. 13026-13029.

Research output: Contribution to journalArticle

Tang, S, Mikala, G, Bahinski, A, Yatani, A, Varadi, G & Schwartz, A 1993, 'Molecular localization of ion selectivity sites within the pore of a human L-type cardiac calcium channel', Journal of Biological Chemistry, vol. 268, no. 18, pp. 13026-13029.
Tang, S. ; Mikala, G. ; Bahinski, A. ; Yatani, A. ; Varadi, G. ; Schwartz, A. / Molecular localization of ion selectivity sites within the pore of a human L-type cardiac calcium channel. In: Journal of Biological Chemistry. 1993 ; Vol. 268, No. 18. pp. 13026-13029.
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AU - Schwartz, A.

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