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
DOI: https://doi.org/10.15407/fz61.04.005
Abstract
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
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