Key Points
- To determine how ischemic preconditioning alters the function and density of cardiac ryanodine receptors and sarcoplasmic reticulum calcium release channels.
- Subjected isolated rat hearts to 30 minutes of global ischemia following preconditioning with three 3-minute or three 1-minute ischemic cycles, evaluated at 5, 120, and 240 minutes post-preconditioning.
- Quantified [3H]ryanodine binding site density and dissociation constant (Kd) in crude ventricular homogenates.
- Measured Ca2+-induced Ca2+ release rate constants in 45Ca-loaded crude homogenates and microsomal fractions using quick filtration.
- Ventricular [3H]ryanodine binding site density significantly decreased from control (372 ± 18 fmol/mg) at 5 minutes (290 ± 15 fmol/mg, P < .01) and 120 minutes (298 ± 17 fmol/mg, P < .05) after preconditioning, recovering by 240 minutes (341 ± 21 fmol/mg) with unchanged binding affinity (Kd = 1.5 ± 0.3 nmol/L).
- Homogenate Ca2+-induced Ca2+ release rate constants dropped from 25.4 ± 1.7 s⁻¹ in controls to 19.7 ± 1.4 s⁻¹ at 5 minutes and 18.9 ± 0.9 s⁻¹ at 120 minutes (P < .05 for both), returning to baseline at 240 minutes (23.0 ± 1.9 s⁻¹).
- Three 1-minute cycles of global ischemia neither protected against 30-minute ischemic injury nor altered ryanodine receptor binding parameters.
Structured PICO
PPopulationIsolated rat heart model
IInterventionPreconditioning ischemia (three 3-minute periods of global ischemia)
CComparatorControl condition or three 1-minute periods of global ischemia
OOutcomeDensity of [3H]ryanodine binding sites and rate constant of Ca(2+)-induced Ca2+ releasesurrogate
Ischemic preconditioning in an isolated rat heart model transiently reduces the density of ryanodine binding sites and the rate of Ca2+-induced Ca2+ release.