Thrombin activity propagates in space during blood coagulation as an excitation wave. 2012

N M Dashkevich, and M V Ovanesov, and A N Balandina, and S S Karamzin, and P I Shestakov, and N P Soshitova, and A A Tokarev, and M A Panteleev, and F I Ataullakhanov
Center for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of Sciences, Moscow, Russia.

Injury-induced bleeding is stopped by a hemostatic plug formation that is controlled by a complex nonlinear and spatially heterogeneous biochemical network of proteolytic enzymes called blood coagulation. We studied spatial dynamics of thrombin, the central enzyme of this network, by developing a fluorogenic substrate-based method for time- and space-resolved imaging of thrombin enzymatic activity. Clotting stimulation by immobilized tissue factor induced localized thrombin activity impulse that propagated in space and possessed all characteristic traits of a traveling excitation wave: constant spatial velocity, constant amplitude, and insensitivity to the initial stimulation once it exceeded activation threshold. The parameters of this traveling wave were controlled by the availability of phospholipids or platelets, and the wave did not form in plasmas from hemophilia A or C patients who lack factors VIII and XI, which are mediators of the two principal positive feedbacks of coagulation. Stimulation of the negative feedback of the protein C pathway with thrombomodulin produced nonstationary patterns of wave formation followed by deceleration and annihilation. This indicates that blood can function as an excitable medium that conducts traveling waves of coagulation.

UI MeSH Term Description Entries
D011486 Protein C A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation.
D011817 Rabbits A burrowing plant-eating mammal with hind limbs that are longer than its fore limbs. It belongs to the family Leporidae of the order Lagomorpha, and in contrast to hares, possesses 22 instead of 24 pairs of chromosomes. Belgian Hare,New Zealand Rabbit,New Zealand Rabbits,New Zealand White Rabbit,Rabbit,Rabbit, Domestic,Chinchilla Rabbits,NZW Rabbits,New Zealand White Rabbits,Oryctolagus cuniculus,Chinchilla Rabbit,Domestic Rabbit,Domestic Rabbits,Hare, Belgian,NZW Rabbit,Rabbit, Chinchilla,Rabbit, NZW,Rabbit, New Zealand,Rabbits, Chinchilla,Rabbits, Domestic,Rabbits, NZW,Rabbits, New Zealand,Zealand Rabbit, New,Zealand Rabbits, New,cuniculus, Oryctolagus
D001777 Blood Coagulation The process of the interaction of BLOOD COAGULATION FACTORS that results in an insoluble FIBRIN clot. Blood Clotting,Coagulation, Blood,Blood Clottings,Clotting, Blood
D005337 Fibrin A protein derived from FIBRINOGEN in the presence of THROMBIN, which forms part of the blood clot. Antithrombin I
D006487 Hemostasis The process which spontaneously arrests the flow of BLOOD from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements (eg. ERYTHROCYTE AGGREGATION), and the process of BLOOD COAGULATION. Hemostases
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001696 Biomechanical Phenomena The properties, processes, and behavior of biological systems under the action of mechanical forces. Biomechanics,Kinematics,Biomechanic Phenomena,Mechanobiological Phenomena,Biomechanic,Biomechanic Phenomenas,Phenomena, Biomechanic,Phenomena, Biomechanical,Phenomena, Mechanobiological,Phenomenas, Biomechanic
D013917 Thrombin An enzyme formed from PROTHROMBIN that converts FIBRINOGEN to FIBRIN. Thrombase,Thrombin JMI,Thrombin-JMI,Thrombinar,Thrombostat,alpha-Thrombin,beta,gamma-Thrombin,beta-Thrombin,gamma-Thrombin,JMI, Thrombin
D018180 Thrombomodulin A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation.

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