Pseudohypoaldosteronism type 1 and Liddle's syndrome mutations that affect the single-channel properties of the epithelial Na+ channel.

These studies test whether three disease-causing mutations in genes (SCNN1A and SCNN1G) encoding subunits of the epithelial Na(+) channel, ENaC, affect the biophysical and gating properties of this important renal ion channel. The S562P missense mutation in αENaC and the K106_S108delinsN mutation in γENaC are associated with pseudohypoaldosteronism type 1 (PHA1). The N530S missense mutation in γENaC causes Liddle's syndrome.

Regulation of Na+ excretion and arterial blood pressure by purinergic signalling intrinsic to the distal nephron: consequences and mechanisms.

Discretionary control of Na(+) excretion is a key component of the regulation of arterial blood pressure in mammals. Sodium excretion is fine-tuned in the aldosterone-sensitive distal nephron by the activity of the epithelial Na(+) channel (ENaC). Here, ENaC functions as a final effector of the renin-angiotensin-aldosterone system (RAAS) during negative feedback control of blood pressure.

Restrictive expression of acid-sensing ion channel 5 (asic5) in unipolar brush cells of the vestibulocerebellum.

Acid-sensing ion channels (Asic) are ligand-gated ion channels in the Degenerin/Epithelial Na+ channel (Deg/ENaC) family. Asic proteins are richly expressed in mammalian neurons. Mammals express five Asic genes: Asic1-5.

Selective inhibition of KCa3.1 channels mediates adenosine regulation of the motility of human T cells.

Adenosine, a purine nucleoside, is present at high concentrations in tumors, where it contributes to the failure of immune cells to eliminate cancer cells. The mechanisms responsible for the immunosuppressive properties of adenosine are not fully understood. We tested the hypothesis that adenosine's immunosuppressive functions in human T lymphocytes are in part mediated via modulation of ion channels.

Patch-clamping Drosophila sensory neurons.

Electrophysiological studies provide essential clues about the regulation and physiological function of ion channel proteins. Probing ion channel activity in vivo, though, often is challenging. This can limit the usefulness of such model organisms as Drosophila for electrophysiological studies.

Inhibition of neuronal degenerin/epithelial Na+ channels by the multiple sclerosis drug 4-aminopyridine.

The voltage-gated K(+) (Kv) channel blocker 4-aminopyridine (4-AP) is used to target symptoms of the neuroinflammatory disease multiple sclerosis (MS). By blocking Kv channels, 4-AP facilitates action potential conduction and neurotransmitter release in presynaptic neurons, lessening the effects of demyelination. Because they conduct inward Na(+) and Ca(2+) currents that contribute to axonal degeneration in response to inflammatory conditions, acid-sensing ion channels (ASICs) contribute to the pathology of MS.

Pickpocket1 is an ionotropic molecular sensory transducer.

The molecular transformation of an external stimulus into changes in sensory neuron activity is incompletely described. Although a number of molecules have been identified that can respond to stimuli, evidence that these molecules can transduce stimulation into useful neural activity is lacking. Here we demonstrate that pickpocket1 (ppk1), a Drosophila homolog of mammalian Degenerin/epithelial sodium channels, encodes an acid-sensing sodium channel that conducts a transient depolarizing current in multidendritic sensory neurons of Drosophila melanogaster.

The role of aspartic acid residues 405 and 416 of the kidney isotype of sodium-bicarbonate cotransporter 1 in its targeting to the plasma membrane.

The NH(2) terminus of the sodium-bicarbonate cotransporter 1 (NBCe1) plays an important role in its targeting to the plasma membrane. To identify the amino acid residues that contribute to the targeting of NBCe1 to the plasma membrane, polarized MDCK cells were transfected with expression constructs coding for green fluorescent protein (GFP)-tagged NBCe1 NH(2)-terminal deletion mutants, and the localization of GFP-tagged proteins was analyzed by confocal microscopy. Our results indicate that the amino acids between residues 399 and 424 of NBCe1A contain important sequences that contribute to its localization to the plasma membrane.

Modulation of Kv1.3 channels by protein kinase A I in T lymphocytes is mediated by the disc large 1-tyrosine kinase Lck complex.

The cAMP/PKA signaling system constitutes an inhibitory pathway in T cells and, although its biochemistry has been thoroughly investigated, its possible effects on ion channels are still not fully understood. K(V)1.3 channels play an important role in T-cell activation, and their inhibition suppresses T-cell function.

Voltage-dependent gating underlies loss of ENaC function in Pseudohypoaldosteronism type 1.

Here we explore the mechanism and associated structure-function implications of loss of function for epithelial Na(+) channel (ENaC) containing a pseudohypoaldosteronism type 1 (PHA-1)-causing missense point mutation. As expected, human ENaC that contained subunits harboring PHA-1-causing substitutions within an absolutely conserved, cytosolic Gly residue (e.g.

Localization of Kv1.3 channels in the immunological synapse modulates the calcium response to antigen stimulation in T lymphocytes.

The immunological synapse (IS), a highly organized structure that forms at the point of contact between a T cell and an APC, is essential for the proper development of signaling events, including the Ca(2+) response. Kv1.3 channels control Ca(2+) homeostasis in human T cells and move into the IS upon Ag presentation.

Intrinsic voltage dependence of the epithelial Na+ channel is masked by a conserved transmembrane domain tryptophan.

Tryptophan residues critical to function are frequently located at the lipid-water interface of transmembrane domains. All members of the epithelial Na+ channel (ENaC)/Degenerin (Deg) channel superfamily contain an absolutely conserved Trp at the base of their first transmembrane domain. Here, we test the importance of this conserved Trp to ENaC/Deg function.

[Nonlinear analysis of the dynamics of the human balance control system during fixation and smooth pursuit of visual target].

The similarity between the dynamics of the human balance control system in the frontal and sagittal planes during the fixation of visual stimulus and smooth pursuit of its sinusoidal movements in the horizontal plane with a frequency of 0.1 or 0.01 Hz (so-named fast and slow pursuit) has been investigated by the nonlinear method of analysis.

[Mathematical modeling of the mechanisms of locomotory pattern formation under epidural spinal cord stimulation with consideration of peripheral feedback].

The mechanisms of nervous regulation of locomotory activity of the spinal cord and participation of afferent peripheral feedback from lower limb muscles in the formation of locomotory patterns were investigated. The set of electromyograms of lower-limb muscle groups recorded in experiments on mesencephalic cats with application of electric epidural stimulations of lumbar segments of the spinal cord is described by a nonlinear dynamic model constructed on the basis of the Van-der-Pol equation with the compelling member. The conditions of occurrence of the regime of self-oscillations were investigated depending on the parameters of external influence.

Formation of locomotor patterns in decerebrate cats in conditions of epidural stimulation of the spinal cord.

Acute experiments on decerebrate cats were performed to study the mechanism of formation of the locomotor pattern in conditions of epidural stimulation of the spinal cord. These studies showed that only segments L3-L5 contributed to generating the stepping pattern in the hindlimbs. At the optimum frequency (5-10 Hz) of stimulation of these segments, formation of electromyographic burst activity in the flexor muscles was mainly due to polysynaptic reflex responses with latencies of 80-110 msec.

[Changes in extracellular K+ concentration modulate properties of voltage dependent K+ channel conductance in PC-12 cells].

The complex processing and integration of signals observed in neurons are facilitated by the diverse range of gating properties of the ion channels in this cell type, particularly the voltage-gated K+ channels (Kv). A distinctive combination of K+ channels endows neurons with a broad repertoire of excitable properties and allows each neuron to respond in a specific manner to a given input at a given time. The properties of many K+ channels can be modulated by second messenger pathways activated by neurotransmitters and other stimuli.

[Features of stepping pattern formation in decerebrated cats under epidural spinal cord stimulation].

The mechanisms of stepping pattern formation initiated by epidural spinal cord stimulation in decerebrated cats, were investigated. It is shown that the ability to produce the stepping pattern involve the L3-L5 segments. In flexor muscle, the formation of stepping pattern under optimal stimulation frequency (5-10 Hz) of these segments is provided by polysynaptic activity with the latency 80-110 ms.

[Mathematical model of the digestion process regulation and its computer presentation].

The article presents a mathematic model, which describes regulation of the digestion process. The simulation was based on data on mutual influence of the factors participating in digestion regulation, which were acquired from analysis of over 1200 sources of experimental observations on digestion in dogs published in Russia and abroad, and on own experimental studies. The simulation includes 67 factors and about 400 interactions observed between them.

[Modulation of voltage-gated sodium channels by recombinant interferon-alpha2b in the human neuroblastoma cell line IMR-32].

Clonal human neuroblastoma cells imr-32 are a suitable model system for studies of neuronal excitability modulation. The ability interferon-alpha 2b "laferon" to modulate the mechanisms of electrical activity was studied in whole-cell patch-clamped undifferentiated human neuroblastoma cells IMR-32. It was shown that 1 h incubation of IMR-32 cells at 37 degrees C in medium with laferon (600 U/ml) exerted changes in voltage-dependent properties of Na(+)-channels.

[The pathogenesis of sepsis and the possibilities for its treatment using nondrug methods].

The substantiation of views to the foci of the "cryptogenic" infection and its nature in sepsis is given. The state of the redox system, immunological status and functions of the liver and kidneys in patients with complicated sepsis are investigated. The data on the influence of nonmedicamental methods (hemodialysis, AUVIB, HBO, EHS) upon the parameters of the redox system, cellular and humoral immunity in acute sepsis patients are presented.

[The pathogenetic and clinical grounds for the advantages of nondrug procedures in the preoperative preparation of patients with diffuse toxic goiter].

An analysis of 615 patients operated upon for diffuse toxic goiter is presented. In 148 of them (24%) preoperative preparation was made with the help of nonmedicamental methods (extracorporal hemosorption, hyperbaric oxygenation (HBO), plasmapheresis). The state of euthyroidism was controlled according to their clinical symptoms and was verified by radioimmunological studies of triiodothyronine (T3), thyroxin (T4), thyrotropine (TTG).