Modulation of Ca²⁺-gated cardiac muscle Ca²⁺-release channel (ryanodine receptor) by mono- and divalent ions

Abstract

The effects of mono- and divalent ions on Ca2+-gated cardiac muscle Ca2+-release channel (ryanodine receptor) activity were examined in [3H]ryanodine-binding measurements. Ca2+ bound with the highest apparent affinity to Ca2+activation sites in choline chloride medium, followed by KCl, CsCl, NaCl, and LiCl media. The apparent Ca2+ binding affinities of Ca2+ inactivation sites were lower in choline chloride and CsCl media than in LiCl, NaCl, and KCl media. Sr2+ activated the ryanodine receptor with a lower efficacy than Ca2+. Competition studies indicated that Li+, K+, Mg2+, and Ba2+ compete with Ca2+ for Ca2+ activation sites. In 0.125 M KCl medium, the Ca2+ dependence of [3H]ryanodine binding was modified by 5 mM Mg2+ and 5 mM β,γ-methyleneadenosine 5′-triphosphate (a nonhydrolyzable ATP analog). The addition of 5 mM glutathione was without appreciable effect. Substitution of Cl−by 2-( N-morpholino)ethanesulfonic acid ion caused an increase in the apparent Ca2+affinity of the Ca2+ inactivation sites, whereas an increase in KCl concentration had the opposite effect. These results suggest that cardiac muscle ryanodine receptor activity may be regulated by 1) competitive binding of mono- and divalent cations to Ca2+ activation sites, 2) binding of monovalent cations to Ca2+ inactivation sites, and 3) binding of anions to anion regulatory sites.

Effect of osmotic stress on spontaneous calcium sparks in rat ventricular myocytes

“…This change seems to be different from the results obtained by single-channel recording [21,22] . The exact reason for this discrepancy is unclear.…”

“…Role of ionic strength Previous studies have indicated that the activity of RyRs and the interaction between RyRs are modulated by ionic strength. For instance, with singlechannel recording an increase of RyR activity has been shown with increasing KCl concentration [21,22] . By photon Each curve was obtained from ≥634 events (Ca 2+ sparks).…”

Inhibition of Ryanodine Binding to Sarcoplasmic Reticulum Vesicles of Cardiac Muscle by Zn²⁺ Ions

“…However, there is a controversy about the existence of CaI on RyR2s [4]. Recently, it is shown that high [Ca 2+ ] f could evidently decrease the binding to the SR of canine heart, indicating the presence of CaI on RyR2s [14]. This proposal is supported by the present study (Fig.…”

Mg2+ activates the ryanodine receptor type 2 (RyR2) at intermediate Ca2+ concentrations

“…We showed clearly the effectiveness of the I-site, although RyR2 shows a lower affinity than RyR1 and RyR3 (Table 1). One explanation for this discrepancy is the difference in experimental conditions: a high salt-medium, 1 M KCl, was used instead of 0.17 M KCl, and/or purified RyR2 was used for the experiments (8,14,15,18,34,37). Another explanation is the limited range of Ca 2ϩ concentrations of up to pCa 4 (14, 15).…”