| Autor: |
Plakhova VB; Pavlov Institute of Physiology of the Russian Academy of Sciences, 6 Makarova Emb., 199034, Saint Petersburg, Russia., Penniyaynen VA; Pavlov Institute of Physiology of the Russian Academy of Sciences, 6 Makarova Emb., 199034, Saint Petersburg, Russia., Rogachevskii IV; Pavlov Institute of Physiology of the Russian Academy of Sciences, 6 Makarova Emb., 199034, Saint Petersburg, Russia., Podzorova SA; Pavlov Institute of Physiology of the Russian Academy of Sciences, 6 Makarova Emb., 199034, Saint Petersburg, Russia., Khalisov MM; Pavlov Institute of Physiology of the Russian Academy of Sciences, 6 Makarova Emb., 199034, Saint Petersburg, Russia., Ankudinov AV; Ioffe Physical Technical Institute, Russian Academy of Sciences, 26 Polytekhnicheskaya str., 194021, Saint Petersburg, Russia., Krylov BV; Pavlov Institute of Physiology of the Russian Academy of Sciences, 6 Makarova Emb., 199034, Saint Petersburg, Russia. |
| Abstrakt: |
In the primary sensory neuron, ouabain activates the dual mechanism that modulates the functional activity of Na V 1.8 channels. Ouabain at endogenous concentrations (EO) triggers two different signaling cascades, in which the Na,K-ATPase/Src complex is the EO target and the signal transducer. The fast EO effect is based on modulation of the Na V 1.8 channel activation gating device. EO triggers the tangential signaling cascade along the neuron membrane from Na,K-ATPase to the Na V 1.8 channel. It evokes a decrease in effective charge transfer of the Na V 1.8 channel activation gating device. Intracellular application of PP2, an inhibitor of Src kinase, completely eliminated the effect of EO, thus indicating the absence of direct EO binding to the Na V 1.8 channel. The delayed EO effect probably controls the density of Na V 1.8 channels in the neuron membrane. EO triggers the downstream signaling cascade to the neuron genome, which should result in a delayed decrease in the Na V 1.8 channels' density. PKC and p38 MAPK are involved in this pathway. Identification of the dual mechanism of the strong EO effect on Na V 1.8 channels makes it possible to suggest that application of EO to the primary sensory neuron membrane should result in a potent antinociceptive effect at the organismal level. |
