Functional Characteristics of the Nav1.1 p.Arg1596Cys Mutation Associated with Varying Severity of Epilepsy Phenotypes.

Mutations of the gene, which encodes the voltage-dependent Na channel's α subunit, are associated with diverse epileptic syndromes ranging in severity, even intra-family, from febrile seizures to epileptic encephalopathy. The underlying cause of this variability is unknown, suggesting the involvement of additional factors. The aim of our study was to describe the properties of mutated channels and investigate genetic causes for clinical syndromes' variability in the family of five gene p.

STIM2 regulates NMDA receptor endocytosis that is induced by short-term NMDA receptor overactivation in cortical neurons.

Recent findings suggest an important role for the dysregulation of stromal interaction molecule (STIM) proteins, activators of store-operated Ca channels, and the prolonged activation of N-methyl-D-aspartate receptors (NMDARs) in the development of neurodegenerative diseases. We previously demonstrated that STIM silencing increases Ca influx through NMDAR and STIM-NMDAR2 complexes are present in neurons. However, the interplay between NMDAR subunits (GluN1, GluN2A, and GluN2B) and STIM1/STIM2 with regard to intracellular trafficking remains unknown.

Activity of TREK-2-like Channels in the Pyramidal Neurons of Rat Medial Prefrontal Cortex Depends on Cytoplasmic Calcium.

TREK-2-like channels in the pyramidal neurons of rat prefrontal cortex are characterized by a wide range of spontaneous activity-from very low to very high-independent of the membrane potential and the stimuli that are known to activate TREK-2 channels, such as temperature or membrane stretching. The aim of this study was to discover what factors are involved in high levels of TREK-2-like channel activity in these cells. Our research focused on the PI(4,5)P2-dependent mechanism of channel activity.

Valproic acid potently inhibits interictal-like epileptiform activity in prefrontal cortex pyramidal neurons.

Valproic acid has a long-standing reputation of effectively treating the symptoms of not only epilepsy but also psychiatric conditions. In the latter, the exact mechanism by which valproate exerts its effect remains unclear. In this study, epileptiform bursts were recorded from pyramidal neurons in the prefrontal cortex (the brain region thought to be involved in psychiatric disorders) using the patch-clamp technique.

Hydrocortisone inhibition of wild-type and αD200Q nicotinic acetylcholine receptors.

Short-term treatment with large doses of corticosteroids can result in acute weakness of muscles in processes that have not yet been fully characterized. Corticosteroids have been shown to exert direct inhibitory action on the muscle-type nicotinic acetylcholine receptor (AChR), and therefore can promote pharmacological muscle denervation. The mechanism of hydrocortisone (HC) blockage of AChR has not been fully established yet.

Age-dependent expression of Nav1.9 channels in medial prefrontal cortex pyramidal neurons in rats.

Developmental changes that occur in the prefrontal cortex during adolescence alter behavior. These behavioral alterations likely stem from changes in prefrontal cortex neuronal activity, which may depend on the properties and expression of ion channels. Nav1.

Valproic acid inhibits TTX-resistant sodium currents in prefrontal cortex pyramidal neurons.

Valproic acid is frequently prescribed and used to treat epilepsy, bipolar disorder and other conditions. However, the mechanism of action of valproic acid has not been fully elucidated. The aim of this study was to assess the influence of valproic acid (200 μM) on TTX-resistant sodium currents in mPFC pyramidal neurons.

The H-loop in the second nucleotide-binding domain of the cystic fibrosis transmembrane conductance regulator is required for efficient chloride channel closing.

The cystic fibrosis transmembrane conductance regulator (CFTR) is an ATP-binding cassette (ABC) transporter that functions as a cAMP-activated chloride channel. The recent model of CFTR gating predicts that the ATP binding to both nucleotide-binding domains (NBD1 and NBD2) of CFTR is required for the opening of the channel, while the ATP hydrolysis at NBD2 induces subsequent channel closing. In most ABC proteins, efficient hydrolysis of ATP requires the presence of the invariant histidine residue within the H-loop located in the C-terminal part of the NBD.

Potassium currents in human myogenic cells from healthy and congenital myotonic dystrophy foetuses.

The whole-cell patch clamp technique was used to record potassium currents in in vitro differentiating myoblasts isolated from healthy and myotonic dystrophy type 1 (DM1) foetuses carrying 2000 CTG repeats. The fusion of the DM1 myoblasts was reduced in comparison to that of the control cells. The dystrophic muscle cells expressed less voltage-activated K(+) (delayed rectifier and non-inactivating delayed rectifier) and inward rectifier channels than the age-matched control cells.

Potassium currents in human myogenic cells from donors of different ages.

Ageing in humans is accompanied by a reduction in the capacity of satellite cells to proliferate and the forming myoblasts to fuse. The processes of myoblast differentiation and fusion are associated with specific changes in the cells electrical properties. We wanted to elucidate the possible effects of ageing on these parameters and performed whole-cell patch-clamp recordings on human myoblasts obtained from biopsies of skeletal muscles from 2-, 48- and 76-year-old donors.

Large-conductance K+ channel openers NS1619 and NS004 as inhibitors of mitochondrial function in glioma cells.

Recently, it has been reported that large-conductance Ca(2+)-activated potassium channels, also known as BK(Ca)-type potassium channels, are present in the inner mitochondrial membrane of the human glioma LN229 cell line. Hence, in the present study, we have investigated whether BK(Ca)-channel openers (BK(Ca)COs), such as the benzimidazolone derivatives NS004 (5-trifluoromethyl-1-(5-chloro-2-hydroxyphenyl)-1,3-dihydro-2H-benzimidazole-2-one) and NS1619 (1,3-dihydro-1-[2-hydroxy-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-2H-benzimidazol-2-one), affect the functioning of LN229 glioma cell mitochondria in situ. We examined the effect of BK(Ca)COs on mitochondrial membrane potential, mitochondrial respiration and plasma membrane potassium current in human glioma cell line LN229.

[Role and function of voltage-gated chloride channels of the CIC family and their defects leading to genetic diseases].

There are 9 channels of the ClC family in mammals and few others in fishes, plants, yeast and bacteria. The ClC channels are present in different tissues and play a role in transmembrane potential stabilization, transepithelial transport, cell volume regulation, acidification of intracellular organelles. The genetic defects of ClC-1 chloride channel lead to myotonias, the defect in ClC-5 channel to the formation of stones in kidney, while the defect in ClC-Kb channel leads to the Bartter's syndrome.

Properties of primary mouse myoblasts expanded in culture.

Implantation of myoblasts is a strategy used to enhance the regeneration of skeletal muscle tissue in vivo. In mouse models, myogenic cell lines and primary cells have been employed with different yields of adult muscle tissue formed. The present work is a study of some developmental features of expanded primary mouse myoblasts (i28), which have been shown to form muscle tissue.

Modulation of acetylcholine receptor channel kinetics by hydrocortisone.

The kinetics of the nicotinic acetylcholine receptor (AChR) channel were analysed in the presence of hydrocortisone (HC, 100-400 microM), an electrically neutral steroid. The channel open time decreased, and in contrast to control conditions did not show any voltage dependency. However, HC induced a new (blocked) component in the closed time distribution, with a time constant that decreased with membrane hyperpolarization.