Dynamics of calcium spiking, mitochondrial collapse and phosphatidylserine exposure in platelet subpopulations during activationстатья
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
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Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 15 ноября 2016 г.
Аннотация:Background
Activated platelets form two subpopulations, one able to efficiently aggregate, while another externalizes phosphatidylserine (PS) and thus accelerates membrane-dependent reactions of blood coagulation. The latter, procoagulant subpopulation is characterized by high cytosolic calcium and loss of inner mitochondrial membrane potential, and there are conflicting opinions on their roles in its formation.
Methods
We used confocal microscopy to investigate dynamics of subpopulation formation by imaging single, fibrinogen-bound platelets with individual mitochondria in them upon loading with calcium-sensitive and mitochondrial potential-sensitive dyes. Stimulation was with thrombin or protease-activated receptor 1 (PAR1) agonist SFLLRN. Stochastic simulations using computational systems biology model of PAR1 calcium signaling were employed for analysis.
Results
Platelet activation resulted in a series of cytosolic calcium spikes and mitochondrial calcium uptake in all platelets. Frequency of spikes decreased with time for SFLLRN stimulation, but remained high for a long period of time for thrombin. In some platelets, uptake of calcium by mitochondria led to the mitochondrial permeability transition pore opening and inner mitochondrial membrane potential loss that could be either reversible or irreversible. The latter resulted in cytosolic calcium rise and PS exposure. These platelets had higher cytosolic calcium before activation, and their mitochondria collapsed not simultaneously but one after another.
Conclusions
These results support a model of procoagulant subpopulation development following a series of stochastic cytosolic calcium spikes that are accumulated by mitochondria leading to a collapse, and suggest important roles of individual platelet reactivity and signal exchange between different mitochondria of a platelet.