Alteration of sarcoplasmic reticulum Ca~(2+) release termination by ryanodine receptor sensitization and in heart failure

摘要

Many physiological processes and pharmacological agents modulate the ryanodine receptor (RyR), the primary sarcoplasmic reticulum (SR) Ca~(2+) release channel in the heart. However, how such modulations translate into functional effects during cardiac excitation-contraction coupling (ECC) is much less clear. Using a low dose (250mum) of caffeine we sensitized the RyR and examined SR Ca~(2+) release using dynamic measurements of cytosolic Ca~(2+) ([Ca~(2+)]_i) and free Ca~(2+) within the SR ([Ca~(2)+ ] _SR). In field stimulated (1 Hz) rabbit ventricular myocytes, application of 250 /mum caffeine caused an initial 33% increase in SR Ca~(2+) release, which was followed by a decrease in SR Ca~(2+) load (28%) and steady-state SR Ca~(2+) release (23%).