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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2015; 61(4): 5-10

Thrombin modulates persistent sodium current in CA1 pyramidal neurons of young and adult rat hippocampus

O.O. Lunko, D.S. Isaev, O.O. Krishtal, E.V. Isaeva

    O.O. Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine


Serine protease thrombin, a key factor of blood coagulation, participates in many neuronal processes important for normal brain functioning and during pathological conditions involving abnormal neuronal synchronization, neurodegeneration and inflammation. Our previous study on CA3 pyramidal neurons showed that application of thrombin through the activation of specific protease-activated receptor 1 (PAR1) produces a significant hyperpolarizing shift of the activation of the TTX-sensitive persistent voltage-gated Na+ current (INaP) thereby affecting membrane potential and seizure threshold at the network level. It was shown that PAR1 is also expressed in CA1 area of hippocampus and can be implicated in neuronal damage in this area after status epilepticus. The aim of the present study was to evaluate the effect of thrombin on INaP in CA1 pyramidal neurons from adult and young rats. Using whole cell patch-clamp technique we demonstrate that thrombin application results in the hyperpolarization shift of INaP activation as well as increase in the INaP amplitude in both age groups. We have found that INaP in pyramidal neurons of hippocampal CA1 region is more vulnerable to the thrombin action than INaP in pyramidal neurons of hippocampal CA3 region. We have also found that the immature hippocampus is more sensitive to thrombin action which emphasizes the contribution of thrombin-dependent pathway to the regulation of neuronal activity in immature brain

Keywords: hippocampus, persistent sodium current, thrombin


  1. Siller-Matula JM, Schwameis M, Blann A, Mannhalter C, Jilma B. Thrombin as a multi-functional enzyme: Focus on in vitro and in vivo effects. Thromb Haemost. 2011; 106:1020–33. CrossRef PubMed
  3. Lukasiuk K, Wilczynski GM, Kaczmarek L. Extracellular proteases in epilepsy. Epilepsy Res. 2011; 96:191–206. CrossRef PubMed
  5. Ramachandran R, Hollenberg MD. Proteinases and signalling: pathophysiological and therapeutic implications via PARs and more. Br J Pharmacol. 2008; 153 Suppl: S263–82.
  7. Almonte AG, Sweatt JD. Serine proteases, serine protease inhibitors, and protease-activated receptors: Roles in synaptic function and behavior. Brain Res. 2011; 1407:107–22. CrossRef PubMed PubMedCentral
  9. Almonte AG, Qadri LH, Sultan F a., Watson J a., Mount DJ, Rumbaugh G, Sweatt JD. Protease-activated receptor-1 modulates hippocampal memory formation and synaptic plasticity. J Neurochem. 2013; 124:109–22. CrossRef PubMed PubMedCentral
  11. Han K-S, Mannaioni G, Hamill CE, Lee J, Junge CE, Lee CJ, Traynelis SF. Activation of protease activated receptor 1 increases the excitability of the dentate granule neurons of hippocampus. Mol Brain. 2011; 4:32. CrossRef PubMed PubMedCentral
  13. Macfarlane SR, Seatter MJ, Kanke T, Hunter GD, Plevin R. Proteinase-Activated Receptors. 2001; 53:245–82.
  15. Niclou SP, Suidan HS, Pavlik A, Vejsada R, Monard D. Changes in the expression of protease-activated receptor 1 and protease nexin-1 mRNA during rat nervous system development and after nerve lesion. Eur J Neurosci. 1998; 10:1590–607. CrossRef PubMed
  17. Xi G, Reiser G, Keep RF. The role of thrombin and thrombin receptors in ischemic, hemorrhagic and traumatic brain injury: Deleterious or protective? J Neurochem. 2003; 84:3–9.
  19. Maggio N, Shavit E, Chapman J, Segal M. Thrombin induces long-term potentiation of reactivity to afferent stimulation and facilitates epileptic seizures in rat hippocampal slices: toward understanding the functional consequences of cerebrovascular insults. J Neurosci. 2008; 28:732–6. CrossRef PubMed
  21. Isaeva E, Hernan A, Isaev D, Holmes GL. Thrombin facilitates seizures through activation of persistent sodium current. Ann Neurol. 2012; 72:192–8. CrossRef PubMed PubMedCentral
  23. 12. Stafstrom CE. Persistent Sodium Current and Its Role in Epilepsy. Epilepsy Curr. 2007; 7:15–22. CrossRef PubMed PubMedCentral
  25. Yamada-Hanff J, Bean BP. Persistent sodium current drives conditional pacemaking in CA1 pyramidal neurons under muscarinic stimulation. J Neurosci. 2013; 33:15011–21. CrossRef PubMed PubMedCentral
  27. Chen S, Su H, Yue C, Remy S, Royeck M, Sochivko D, Opitz T, Beck H, Yaari Y. An increase in persistent sodium current contributes to intrinsic neuronal bursting after status epilepticus. J Neurophysiol. 2011; 105:117–29. CrossRef PubMed
  29. Isaev D, Lushnikova I, Lunko O, Zapukhliak O, Maximyuk O, Romanov A, Skibo GG, Tian C, Holmes GL, Isaeva E. Contribution of protease-activated receptor 1 in status epilepticus-induced epileptogenesis. Neurobiol Dis. 2015; 78:68–76. CrossRef PubMed PubMedCentral
  31. Kubova H, Lukasiuk K, Pitkänen A. New Insight on the Mechanisms of Epileptogenesis in the Developing Brain. 2012; 3–44.
  33. Lunko O, Isaev D, Maximyuk O, Ivanchick G, Sydorenko V, Krishtal O, Isaeva E. Persistent sodium current properties in hippocampal CA1 pyramidal neurons of young and adult rats. Neurosci Lett. 2014; 559:30–3. CrossRef PubMed
  34.   Lun'ko OO, Isaiev DS, Maxymiuk OP, Kryshtal' OO, Isaieva OV. The effect of enzymatic treatment using proteases on properties of persistent sodium current in CA1 pyramidal neurons of rat hippocampus. Fiziol Zh. 2014; 60:75–9. [Ukrainian]  
  35. Vorobjev VS. Vibrodissociation of sliced mammalian nervous tissue. J Neurosci Methods. 1991; 38:145–50. CrossRef  
  36. Neher E. Correction for liquid junction potentials in patch clamp experiments. Methods Enzymol. 1992; 207:123–31. CrossRef  
  37. Weinstein JR, Gold SJ, Cunningham DD, Gall CM. Cellular localization of thrombin receptor mRNA in rat brain: expression by mesencephalic dopaminergic neurons and codistribution with prothrombin mRNA. J Neurosci. 1995; 15:2906–19.
  39. Aracri P, Colombo E, Mantegazza M, Scalmani P, Curia G, Avanzini G, Franceschetti S. Layer-specific properties of the persistent sodium current in sensorimotor cortex. J Neurophysiol. 2006; 95:3460–8. CrossRef PubMed
  41. Agrawal N, Alonso A, Ragsdale DS. Increased Persistent Sodium Currents in Rat Entorhinal Cortex Layer V Neurons in a Post-Status Epilepticus Model of Temporal Lobe Epilepsy. Epilepsia. 2003; 44:1601–4. CrossRef PubMed
  43. Maggio N, Cavaliere C, Papa M, Blatt I, Chapman J, Segal M. Thrombin regulation of synaptic transmission: Implications for seizure onset. Neurobiol Dis. 2013; 50:171–8. CrossRef PubMed

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