A cardiac dihydropyridine receptor II-III loop peptide inhibits restings Ca2+ sparks in ferret ventricular myocytes

Yanxia Li, Donald M Bers

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

1. We studied the effect of a peptide (Ac-10C) on cardiac ryanodine receptor (RyR) opening. This decapeptide (KKERKLARTA) is a fragment of the cardiac dihydropyridine receptor (DHPR) from the cytosolic loop between the second and third transmembrane domains (II-III loop). Studies were carried out in ferret ventricular myocytes by simultaneously applying ruptured-patch voltage clamp and line-scan confocal microscopy with fluo-3 to measure intracellular [Ca2+] ([Ca2+]i) and Ca2+ sparks. 2. Inclusion of Ac-10C in the dialysing pipette solution inhibited resting Ca2+ spark frequency (due to diastolic RyR openings) by > 50%. This occurred without changing sarcoplasmic reticulum (SR) Ca2+ content, which was measured via the caffeine-induced Ca2+ transient amplitude and the caffeine-induced Na+-Ca2+ exchange current (INCX) integral. Ac-10C also reduced slightly the size of Ca2+ sparks. 3. Ac-10C did not alter either resting [Ca2+]i (assessed by indo-1 fluorescence) or DHPR gating (measured as L-type Ca2+ current). 4. The SR Ca2+ fractional release was depressed by Ac-10C at relatively low SR Ca2+ content, but not at higher SR Ca2+ content. 5. A control scrambled peptide (Ac-10CS) did not alter any of the measured parameters (notably Ca2+ spark frequency or SR Ca2+ fractional release). Thus, the Ac-10C effects may be sequence or charge distribution specific. 6. Our results suggest an inhibitory regulation of RyRs at rest via the cardiac DHPR II-III loop N-terminus region. The mechanism of the effect and whether this interaction is important in cardiac excitation-contraction coupling (E-C coupling) per se, requires further investigation.

Original languageEnglish (US)
Pages (from-to)17-26
Number of pages10
JournalJournal of Physiology
Volume537
Issue number1
DOIs
StatePublished - Nov 15 2001
Externally publishedYes

ASJC Scopus subject areas

  • Physiology

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