| Autor: |
Menzikov SA; Institute of General Pathology and Pathophysiology, Russian Academy of Sciences, 8, Baltiyskaya St., 125315 Moscow, Russia., Zaichenko DM; Institute of General Pathology and Pathophysiology, Russian Academy of Sciences, 8, Baltiyskaya St., 125315 Moscow, Russia., Moskovtsev AA; Institute of General Pathology and Pathophysiology, Russian Academy of Sciences, 8, Baltiyskaya St., 125315 Moscow, Russia.; Russian Medical Academy of Postdoctoral Education, Federal State Budgetary Educational Institution of Further Professional Education of the Ministry of Healthcare of the Russian Federation, 2/1, Barrykadnaya St., 125993 Moscow, Russia., Morozov SG; Institute of General Pathology and Pathophysiology, Russian Academy of Sciences, 8, Baltiyskaya St., 125315 Moscow, Russia., Kubatiev AA; Institute of General Pathology and Pathophysiology, Russian Academy of Sciences, 8, Baltiyskaya St., 125315 Moscow, Russia.; Russian Medical Academy of Postdoctoral Education, Federal State Budgetary Educational Institution of Further Professional Education of the Ministry of Healthcare of the Russian Federation, 2/1, Barrykadnaya St., 125993 Moscow, Russia. |
| Abstrakt: |
γ-Aminobutyric acid type A receptors (GABA A Rs) mediate primarily inhibitory synaptic transmission in the central nervous system. Following fast-paced activation, which provides the selective flow of mainly chloride (Cl - ) and less bicarbonate (HCO 3 - ) ions via the pore, these receptors undergo desensitization that is paradoxically prevented by the process of their recovery, referred to as resensitization. To clarify the mechanism of resensitization, we used the cortical synaptoneurosomes from the rat brain and HEK 293FT cells. Here, we describe the effect of γ-phosphate analogues (γPAs) that mimic various states of ATP hydrolysis on GABA A R-mediated Cl - and HCO 3 - fluxes in response to the first and repeated application of the agonist. We found that depending on the presence of bicarbonate, opened and desensitized states of the wild or chimeric GABA A Rs had different sensitivities to γPAs. This study presents the evidence that recovery of neuronal Cl - and HCO 3 - concentrations after desensitization is accompanied by a change in the intracellular ATP concentration via ATPase performance. The transition between the desensitization and resensitization states was linked to changes in both conformation and phosphorylation. In addition, the chimeric β3 isoform did not exhibit the desensitization of the GABA A R-mediated Cl - influx but only the resensitization. These observations lend a new physiological significance to the β3 subunit in the manifestation of GABA A R resensitization. |
