Microdomain Ca2+ near ryanodine receptors as reported by L-type Ca2+ and Na+/Ca2+ exchange currents

摘要

Non-technical summaryThe strength of the heart beat is regulated by a short-lived increase of calcium in the cardiac muscle cells. This calcium concentration is assumed to rise particularly high in microdomains where it modulates calcium-dependent processes and controls calcium release from the intracellular store. However, direct measurement of microdomain calcium remains a technical challenge. We have used as reporters the ionic currents from L-type Ca²⁺ channels and from the Na⁺/Ca²⁺ exchanger, proteins that are located in these microdomains and sensitive to local calcium. Microdomain calcium has a much sharper rise and fall than the global calcium signal and its amplitude is 20–30 times higher. Surprisingly, for different global signals, the microdomain signal remained equally high. These findings show the feasibility of reporting on microdomain calcium and demonstrate the divergence between microdomain and global calcium signals.