[Frequency and the mutation spectrum of GJB2-related disorders of hearing in children from Dagestan as compared with the central European part of Russia].

The sequencing of the entire coding region and the donor site of the splicing of the GJB2 gene has shown that prelingual neurosensory nonsyndromic autosomal recessive deafness/poor hearing in Republic Dagestan is genetically more heterogeneous than in the central European part of Russia. Thus, the number of the revealed mutations in the GJB2 gene in Dagestan was only 28% of the total number of alleles in patients tested. The main mutations in the GJB2 gene in Dagestan were represented by three forms typical for West Asia: 35delG mutation (22% of all mutant alleles), deltaE120 mutation (22%), both in the coding region, and IVS 1+1 G > A (44%) in the donor site of splicing. In addition, a novel mutation, deltaE187, was revealed in the coding region. All mutations were found in a compound heterozygous or a heterozygous state. This result allows one to explain the deafness/poor hearing by pathogenic mutations in the GJB2 gene only in 19% of Dagestan families with neurosensory nonsyndromic autosomal recessive disorders of hearing. We suggest that the origin and maintenance of the allele diversity of inherited deafness/poor hearing in Dagestan can be explained by the national and cultural peculiarities of small populations of nations of North Caucasus.

[Allosteric plasticity of GABA(A)-receptor and intraneuronal integration by way of transduction signal].

In work the molecular structure and function of GABA(A)-receptor, dependence of allosteric regulation features from subunit composition of receptors are described. Processes of GABAA-receptor plasticity at kindling are described. The process of GABA(A)-receptor allosteric plasticity by pentylenetetrazole (PTZ) kindling induced automodification of receptor activity and consolidated (keeps by means of updating of an expression of genes) its activity. In some days activity of a receptor is restored to a test objective level. In 6 months PTZ subconvulsive dose administration of kindling rats reproduced the severity of seizures and restored of GABA(A)-receptor activity to the level found 6 months before, at the time of termination of kindling, independent of receptor presence activity and age changes. GABA(A)-receptor activity is consolidated by modification of receptor molecule, it is probably by receptor subunit compositions. The study of learning, memory and PTZ amnesia processes have allowed to make a conclusion that similar mechanisms of GABA(A)-receptor plasticity underlie of learning and memory processes. On the basis of the described results the scheme of intraneuronal modulators integration or integration of transduction signals are described.

[Interaction of local anesthetics with bilayer phospholipid membranes]. / Vzaimodeistvie lokal'nykh anestetikov s bisloinymi fosfolipidnymi membranami.

Local anesthetics--cocaine, lidocaine, novocaine were tested for conductivity of bilayer lipid membranes containing anion-selective channels formed by polyene antibiotic amphotericin B. It has been shown that 5 X 10(-4) M cocaine doubles the membrane conductance. The line of efficiency of the tested anesthetics is: cocaine greater than lidocaine greater than novocaine. Possible molecular mechanism of the discovered effect is discussed.