The Influence of Ca2+ Buffers on Free [Ca2+] Fluctuations and the Effective Volume of Ca2+ Microdomains

摘要: Intracellular calcium (Ca2+) plays a significant role in many cell signaling pathways, some of which are localized to spatially restricted microdomains. Ca2+ binding proteins (Ca2+ buffers) play an important regulating concentration ([Ca2+]). Buffers typically slow [Ca2+] temporal dynamics and increase the effective volume domains. Because fluctuations decrease proportion square-root domain’s physical volume, one might conjecture that buffers and, consequently, mitigate significance small domain concerning signaling. We test this hypothesis through mathematical computational analysis idealized buffer-containing domains their stochastic during free influx with passive exchange both buffer bulk concentrations. derive Langevin equations for fluctuating use these differential determine magnitude different parameters (e.g., dissociation constant concentration). In marked contrast expectations based on naive application principle as employed deterministic models signaling, we find mobile rapid periods influx, whereas stationary (immobile) do not. Also contrary expectations, absence influence characteristics, but not magnitude, fluctuations. analytical formula describing importantly, identify analog (deterministic) volume. Our results demonstrate alter nonintuitive manner. The finding suppress intrinsic raises intriguing question whether or physiologically aspect local