Identification of a peptide inhibitor of the cardiac sarcolemmal Na+-Ca2+ exchanger

Zhaoping Li, Debora A. Nicoll, Anthony Collins, Donald W. Hilgemann, Adelaida G. Filoteo, John T. Penniston, James N. Weise, John M. Tomich, Kenneth D. Philipson

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Abstract

The deduced amino acid sequence of the cardiac sarcolemmal Na+-Ca2+ exchanger has a region which could represent a calmodulin binding site. As calmodulin binding regions of proteins often have an autoinhibitory role, a synthetic peptide with this sequence was tested for functional effects on Na+-Ca2+ exchange activity. The peptide inhibits the Na+-dependent Ca2+ uptake (K1 ∼ 1.5 μM) and the Na+ o-dependent Ca2+ efflux of sarcolemmal vesicles in a noncompetitive manner with respect to both Na+ and Ca2+. The peptide is also a potent inhibitor (K1 ∼ 0.1 μM) of the Na+-Ca2+ exchange current of excised sarcolemmal patches. The binding site for the peptide on the exchanger is on the cytoplasmic surface of the membrane. The exchanger inhibitory peptide binds calmodulin with a moderately high affinity. From the characteristics of the inhibition of the exchange of sarcolemmal vesicles, we deduce that only inside-out sarcolemmal vesicles participate in the usual Na+-Ca2+ exchange assay. This contrasts with the common assumption that both inside-out and right-side-out vesicles exhibit exchange activity.

Original languageEnglish (US)
Pages (from-to)1014-1020
Number of pages7
JournalJournal of Biological Chemistry
Volume266
Issue number2
StatePublished - Jan 15 1991

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Calmodulin
Peptides
Binding Sites
Calmodulin-Binding Proteins
Amino Acid Sequence
Assays
Cell Membrane
Membranes
Amino Acids
Proteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

Li, Z., Nicoll, D. A., Collins, A., Hilgemann, D. W., Filoteo, A. G., Penniston, J. T., ... Philipson, K. D. (1991). Identification of a peptide inhibitor of the cardiac sarcolemmal Na+-Ca2+ exchanger. Journal of Biological Chemistry, 266(2), 1014-1020.

Identification of a peptide inhibitor of the cardiac sarcolemmal Na+-Ca2+ exchanger. / Li, Zhaoping; Nicoll, Debora A.; Collins, Anthony; Hilgemann, Donald W.; Filoteo, Adelaida G.; Penniston, John T.; Weise, James N.; Tomich, John M.; Philipson, Kenneth D.

In: Journal of Biological Chemistry, Vol. 266, No. 2, 15.01.1991, p. 1014-1020.

Research output: Contribution to journalArticle

Li, Z, Nicoll, DA, Collins, A, Hilgemann, DW, Filoteo, AG, Penniston, JT, Weise, JN, Tomich, JM & Philipson, KD 1991, 'Identification of a peptide inhibitor of the cardiac sarcolemmal Na+-Ca2+ exchanger', Journal of Biological Chemistry, vol. 266, no. 2, pp. 1014-1020.
Li Z, Nicoll DA, Collins A, Hilgemann DW, Filoteo AG, Penniston JT et al. Identification of a peptide inhibitor of the cardiac sarcolemmal Na+-Ca2+ exchanger. Journal of Biological Chemistry. 1991 Jan 15;266(2):1014-1020.
Li, Zhaoping ; Nicoll, Debora A. ; Collins, Anthony ; Hilgemann, Donald W. ; Filoteo, Adelaida G. ; Penniston, John T. ; Weise, James N. ; Tomich, John M. ; Philipson, Kenneth D. / Identification of a peptide inhibitor of the cardiac sarcolemmal Na+-Ca2+ exchanger. In: Journal of Biological Chemistry. 1991 ; Vol. 266, No. 2. pp. 1014-1020.
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