Voltage-gated sodium channels are critical for the generation and propagation of electrical signals in most excitable cells. Activation Na+ initiates an action potential, fast inactivation facilitates repolarization membrane by outward K+ current. Fast is also main determinant refractory period between successive impulses. Although voltage sensor domain IV (DIV) has been implicated inactivation, it remains unclear whether activation DIV alone sufficient to occur. Here, we functionally...

The complexes cis-[Ru(phen)2(Apy)2]2+, Apy = 4-aminopyridine and 3,4-aminopyridine, are stable in aqueous solution with strong visible absorption. They present emission the region long lifetime that accumulates cytoplasm of Neuro2A cell line without appreciable cytotoxicity. also serve as mixed-type reversible inhibitors human AChE BuChE high active site contact. cis-[Ru(phen)2(3,4Apy)2]2+ competes efficiently DMPO by OH• radical. Luminescence using fluorescence imaging (FLIM) enables...

Abstract Anoplin, an antimicrobial, helical decapeptide from wasp venom, looses its biological activities by mere deamidation of C ‐terminus. Secondary structure determination, circular dichroism spectroscopy in amphipathic environments, and lytic activity zwitterionic anionic vesicles showed quite similar results for the amidated carboxylated forms peptide. The ‐terminus introduced a negative charge at all‐positive charged peptide, causing loss amphipathicity, as indicated molecular...

Voltage-dependent ion channels are crucial for generation and propagation of electrical activity in biological systems. The primary mechanism voltage transduction these proteins involves the movement a voltage-sensing domain (D), which opens gate located on cytoplasmic side. A distinct conformational change selectivity filter near extracellular side has been implicated slow inactivation gating, is important spike frequency adaptation neural circuits. However, it remains an open question...

The hallmark of many intracellular pore blockers such as tetra-alkylammonium compounds and local anesthetics is their ability to allosterically modify the movement voltage sensors in voltage-dependent ion channels. For instance, sensor domain III specifically stabilized activated state when sodium currents are blocked by anesthetics. molecular mechanism underlying this long-range interaction between blocker-binding site remains poorly understood. Here, using scanning mutagenesis combination...

Antimicrobial peptides appear among innovative biopolymers with potential therapeutic interest. Nevertheless, issues concerning efficiency, production costs, and toxicity persist. Herein, we show that conjugation of chitosans can represent an alternative in the search for these needs. To increase solubility, deacetylated degraded were prepared. Then, they functionalized via N-succinimidyl- S-acetylthiopropionate or glutathione (GSH), endogenous peptide linker. best our knowledge, it is first...

This study shows that MP-1, a peptide from the venom of Polybia paulista wasp, is more toxic to human leukemic T-lymphocytes than primary lymphocytes. By using model membranes and electrophysiology measurements investigate molecular mechanisms underlying this selective action, porelike activity MP-1 was identified with several bilayer compositions. The highest average conductance found in bilayers formed by phosphatidylcholine or mixture phosphatidylserine (70:30). presence cholesterol...

In the last decade, there has been renewed interest in biologically active peptides fields like allergy, autoimmune diseases and antibiotic therapy. Mast cell degranulating mimic G-protein receptors, showing different activity levels even among homologous peptides. Another important feature is their ability to interact directly with membrane phospholipids, a fast concentration-dependent way. The mechanism of action peptide HR1 on model membranes was investigated comparatively other mast...

Jelleines are four naturally occurring peptides that comprise approximately eight or nine C-terminal residues in the sequence of major royal jelly protein 1 precursor (Apis mellifera). The difference between these is limited to one residue sequence, but this has a significant impact their efficacy as antimicrobials. In peptide-bilayer experiments, we demonstrated lytic, pore-forming activity Jelleine-I similar other cationic antimicrobial peptides, which exhibit stronger on anionic bilayers....

Solid tumors tend to have a more glycolytic metabolism leading an accumulation of acidic metabolites in their cytosol, and consequently, intracellular pH (pHi) turns critically lower if the cells do not handle acid excess. Recently, it was proposed that voltage gated proton channels (HV1) can regulate pHi several cancers. Here we report functional expression human glioblastoma multiforme (GBM) cell line, most common lethal brain tumor. T98G presented outward, slow activating...

Voltage-gated potassium (KV) channels regulate diverse physiological processes and are an important target for developing novel therapeutic approaches. Sea anemone (Cnidaria, Anthozoa) venoms comprise a highly complex mixture of peptide toxins with selective pharmacology on KV channels. From the nematocysts sea Actinia bermudensis, that we named AbeTx1 was purified functionally characterized 12 different subtypes (KV1.1⁻KV1.6; KV2.1; KV3.1; KV4.2; KV4.3; KV11.1; and, Shaker IR), three...

The effect of palmitic acid (PA) and oleic (OA) on electrical parameters planar membranes was studied. We found a substantial difference between the effects PA OA proton transfer. induced small increase in conductance, requiring new technique for estimating proton-mediated currents across low-conductance bilayers which an electrometer is used to measure transmembrane current under virtual short circuit (SCC). Open-circuit voltage SCC were determine leak conductances. caused marked membrane...

Abstract Endocannabinoids are amphiphilic molecules that play crucial neurophysiological functions acting as lipid messengers. Antagonists and knockdown of the classical CB1 CB2 cannabinoid receptors do not completely abolish many endocannabinoid activities, supporting idea a mechanism independent whose mode action remains unclear. Here we combine gramicidin A (gA) single channel recordings membrane capacitance measurements to investigate bilayer-modifying activity endocannabinoids. Single...

An important challenge for both students and teachers of physiology is to integrate the different areas in which physiological knowledge didactically divided. In developing countries, such an issue even more demanding, because budget restrictions often affect program with laboratory classes being first on list when it comes cuts expenses. With aim addressing this kind problem, graduate our department organized a summer course offered undergraduate students. The objective was present systems...