Biologičeskie membrany

Neurotrauma is among the main causes of human disability and mortality. However, the mechanisms that mediate the survival and death of cells in the peripheral nervous system are still not fully understood. The transcription factors p53 and E2F1 are the master regulators of basic cellular functions, including DNA repair, cell cycle, metabolism, and apoptosis. Overexpression of p53 and E2F1, shown in a number of experimental models of peripheral nerve injury, suggests an important role of these proteins in the pathogenesis of neurotrauma. This review discusses the epigenetic mechanisms of p53 and E2F1 activation and regulation, which may contribute to the survival or death of neurons and glial cells after traumatic injury. Prospects for further studies of the mechanisms of regulation of the p53 and E2F1 proteins, including those involving histone deacetylases, for the development of neuroprotectors are considered.

In this work, we analyzed the role of voltage-gated (K_V), calcium-activated (K_Ca), and inward-rectifier potassium channels (K_ir) in the effects of hydrogen sulphide (H₂S) donor sodium hydrosulphide (NaHS) on the spontaneous contractile activity of the rat jejunum. Experiments were performed on jejunum segments under isometric contraction conditions. It was shown that NaHS reduced the basal tension of the segments, the amplitude, and the frequency of spontaneous contractions in a dose-dependent manner (10–500 μM); the half-effective concentration (EC50) of the inhibitory effect of NaHS on amplitude was 165 μM. The K_V channel blocker 4-AP (200 µM) increased the amplitude of spontaneous contractions and subsequent application of NaHS (200 μM) suppressed the amplitude and frequency of spontaneous activity as well as in the control; the effect on tonic tension was less pronounced. TEA (3 mM), a non-specific blocker, and paxillin (1 µM), a specific blocker of large conductance K_Са (ВK) channels, increased the amplitude of spontaneous contractions, while the inhibitory effect of NaHS was completely preserved. The selective blocker of small conductance K_Ca (SK) channels NS8593 (4 μM) did not affect the tension and the parameters of spontaneous contractions and did not prevent the effects of NaHS. Diazoxide (100 μM), the opener of К_ATP channels, caused a decrease in the basal tone, the amplitude and frequency of spontaneous contractions. Diazoxide and K_ATP channel blocker glibenclamide (50 μM) prevented the effects of NaHS on the basal tone. The K_ir-channel blocker BaCl₂ (30 µM) increased the amplitude of spontaneous contractions and eliminated the inhibitory effects of NaHS on the frequency and amplitude of spontaneous contractions, and the basal tension decrease was less pronounced compared to control. Thus, a decrease in the tonic tension of a rat jejunum preparation under the action of an H₂S donor is associated with the activation of K_ir, including К_ATP channels, while the effects of H₂S on the amplitude and frequency of spontaneous contractions are mediated by an increase in Ba²⁺-sensitive conductance.

Using the immunofluorescence confocal microscopy, we detected the following GABAergic structures in the somatic muscle of the body wall of the earthworm: neurotransmitter gamma-aminobutyric acid (GABA); the enzyme responsible for synthesis of GABA, glutamate decarboxylase; type 1, 2, and 3 membrane transporters of GABA providing its reuptake; pre- and postsynaptic type A (ionotropic) and type B (metabotropic) GABA receptors. These structures are localized in the areas of cholinergic neuromuscular synapses. We assume that GABA can participate in modulation of motor activity of the earthworm somatic muscles both at pre- and postsynaptic levels of cholinergic neuromuscular synapses.

Reportedly, the innate and adaptive immunity molecules can modulate the synaptic activity of the central nervous system. Interferons are widely used in the treatment of oncological and viral diseases. Even though interferons are classified as ototoxic substances, the mechanism of their effect on the synaptic activity of the inner ear remains unexplored. Here, we analyzed modulating influences of interferon α2b (IFN-α2b) on the function of afferent glutamatergic synapse in the conditions of drug application to the synaptic zone. The experiments were performed on the isolated vestibular apparatus of a frog (Rana temporaria) using an electrophysiological method. IFN-α2b (0.2–40 ng/mL) caused an increase in the background pulse activity of afferent fibers, followed by a decrease in the frequency of discharges, usually at high concentrations of the interferon. Besides, IFN-α2b decreased the glutamate (L-Glu) evoked response and modulated the level of afferent fiber activity restored by L-Glu under the conditions of blockade of the glutamate release from hair cells in hyper-Mg²⁺ and hypo-Ca²⁺ solution. This suggests the postsynaptic effect of IFN-α2b. The presented data indicate the neuromodulating effect of interferon on the synaptic activity of the afferent synapse of the vestibular apparatus.