Training-Induced Sarcoplasmic Reticulum Ca2+ Unloading Occurs without Ca2+ Influx

INTRODUCTION: Aerobic exercise training elicits adaptations in coronary smooth muscle that result in a novel intracellular Ca2+ signaling phenomenon termed sarcoplasmic reticulum (SR) Ca2+ unloading. Sarcoplasmic reticulum Ca2+ unloading is defined as a time-dependent depletion and then repletion of the caffeine-sensitive SR Ca2+ store. PURPOSE: To determine whether Ca2+ influx is necessary to elicit SR Ca2+ unloading. METHODS: Male, Yucatan swine (8 months old) were maintained: 1) sedentary or 2) exercise trained (treadmill running performed 5 d.wk(-1) for 16 wk). Smooth muscle cells were isolated from the right coronary artery and loaded with the intracellular Ca2+-indicator, fura-2. Sarcoplasmic reticulum Ca2+ content was assessed as the change in the caffeine (5 mM)-induced intracellular Ca2+ peak after a 2-, 5-, 8-, 11- or 13-min recovery from high K+ (depolarization)-induced Ca2+ influx in a physiological (2 mM) Ca2+ solution. The effect of Ca2+ influx on SR Ca2+ unloading was assessed by replacing the 2 mM Ca2+ solution with a virtually Ca2+-free (100 nM) solution during the recovery period. RESULTS: Consistent with previous studies, SR Ca2+ unloading was not observed in cells from sedentary swine. In cells from exercise-trained swine, SR Ca2+ depletion was observed in both the 2 mM and Ca2+-free solutions, suggesting that Ca2+-induced Ca2+ release was not initiating SR Ca2+ unloading during the recovery period. In addition, the reloading of the SR Ca2+ store occurred even in the Ca2+-free solution, suggesting that exercise training facilitates an internal cycling of Ca2+ between the SR and another intracellular Ca2+ store. CONCLUSION: In coronary smooth muscle from male swine, Ca2+ influx is not necessary for the exercise training-induced phenomenon, SR Ca2+ unloading.