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Modulation of Cardiac Ryanodine Receptor Channels by Alkaline Earth Cations

Figure 5

Effect of cytosolic Mg²⁺/Ba²⁺ on the behavior of RyR2 exposed to luminal Mg²⁺/Ba²⁺. (A)

Multiple-channel recording of nine RyR2 exposed to 2 µM [Ca²⁺]_cyt with 50 mM luminal Mg²⁺ as current carrier (V_m = 0 mV) before (top) and after (bottom) addition of 1 mM cytosolic Mg²⁺. (B) Chart summarizing mean open probabilities (± S.E.M.) as a function of holding voltage of channels bathed with luminal Mg²⁺ under the indicated cytosolic conditions (n = 9 experiments). (C) Single-channel recording of a RyR2 exposed to 2 µM [Ca²⁺]_cyt with 50 mM luminal Ba²⁺ as current carrier (V_m = 0 mV) before (top) and after (bottom) addition of 250 µM cytosolic Ba²⁺. (D) Mean open probabilities (± S.E.M.) as a function of holding voltage of channels bathed with luminal Ba²⁺ before (filled circles) and after (open circles) addition of 250 µM cytosolic Ba²⁺ (n = 8 experiments). (E) Dwell open time distribution histograms of a single RyR2 exposed to luminal Ba²⁺ in the presence (grey outline) or absence (black outline) of 250 µM cytosolic Ba²⁺. Openings in the absence of cytosolic Ba²⁺ distributed with τ^o₁ = 1.61 ± 0.17 ms (85% events) and τ^o₂ = 6.18 ± 0.83 ms (15%). In the presence of cytosolic Ba²⁺, values were τ^o₁ = 1.09 ± 0.21 ms (70%) and τ^o₂ = 4.25 ± 0.36 ms (30%). (F) Dwell close time distribution histograms of RyR2 bathed with luminal Ba²⁺ before (black outline) and after (grey outline) addition of 250 µM cytosolic Ba²⁺. Closures in the absence of cytosolic Ba²⁺ distributed with τ^c₁ = 0.79 ± 0.24 ms (80% events) and τ^c₂ = 2.95 ± 0.57 ms (20%). In the presence of cytosolic Ba²⁺, values were τ^c₁ = 2.54 ± 0.12 ms (72%) and τ^c₂ = 13.37 ± 0.29 ms (28%)

doi: https://doi.org/10.1371/journal.pone.0026693.g005