Scorpion venom contains different toxins with multiple biological functions. IMe-AGAP is the first Analgesic-Antitumor like Peptide (AGAP) isolated from Iranian scorpion Mesobuthus eupeus. This peptide is similar to AGAP toxin with high analgesic activity, extracted from Chinese scorpion and inhibits NaV1.8 and NaV1.9 voltage-gated sodium channels involved in the ...

Many idiopathic epilepsy syndromes have a characteristic age dependence, the underlying molecular mechanisms of which are largely unknown. Here we propose a mechanism that can explain that epileptic spells in benign familial neonatal-infantile seizures occur almost exclusively during the first days to months of life. Benign familial neonatal-infantile seizures are caused by mutations in the gen...

Many large organic cations are potent blockers of K(+) channels and other cation-selective channels belonging to the P-region superfamily. However, the mechanism by which large hydrophobic cations enter and exit the narrow pores of these proteins is obscure. Previous work has shown that a conserved Lys residue in the DEKA locus of voltage-gated Na(+) channels is an important determinant of Na(+...

Voltage-dependent Na(+) channels are crucial for electrical signalling in excitable cells. Membrane depolarization initiates asynchronous movements in four non-identical voltage-sensing domains of the Na(+) channel. It remains unclear to what extent this structural asymmetry influences pore gating as compared with outwardly rectifying K(+) channels, where channel opening results from a final co...

Voltage-gated Na(+) channels (Na(+) channels) mediate the rising phase of action potentials in neurons and excitable cells. Nine subtypes of the alpha subunit (Na(v)1.1-Na(v)1.9) have been shown to form functional Na(+) channels to date. Recently, anesthetic concentrations of volatile anesthetics and ethanol were reported to inhibit Na(+) channel functions, but it is not known whether all subty...

The use of mesenchymal stromal cells (MSCs) differentiated toward a smooth muscle cell (SMC) phenotype may provide an alternative for investigators interested in regenerating urinary tract organs such as the bladder where autologous smooth muscle cells cannot be used or are unavailable. In this study we measured the effects of good manufacturing practice (GMP)-compliant expansion followed by my...

The molecular mechanisms underlying the differentiation of neural progenitor cells (NPCs) remain poorly understood. In this study we investigated the role of Ca(2+) and cAMP (cyclic adenosine monophosphate) in the differentiation of NPCs extracted from the subventricular zone of E14.5 rat embryos. Patch clamp recordings revealed that increasing cAMP-signaling with Forskolin or IBMX (3-isobutyl-...

ProTx-II, an inhibitory cysteine knot toxin from the tarantula Thrixopelma pruriens, inhibits voltage-gated sodium channels. Using the cut-open oocyte preparation for electrophysiological recording, we show here that ProTx-II impedes movement of the gating charges of the sodium channel voltage sensors and reduces maximum activation of sodium conductance. At a concentration of 1 microM, the toxi...

The excitability of sensory neurons depends on the expression of various voltage-gated Na+ channel isoforms. The tetrodotoxin-resistant (TTXr) Na+ channel Na(v)1.8 accounts for the electroresponsiveness of nociceptive neurons and contributes to inflammatory and neuropathic pain. Na+ channel blockers are clinically employed for chronic pain management, but side effects limit their use. There is ...

Voltage-dependent ion channels are fundamental to the physiology of excitable cells because they underlie the generation and propagation of the action potential and excitation-contraction coupling. To understand how ion channels work, it is important to determine their structures in different conformations in a membrane environment. The validity of the crystal structure for the prokaryotic K(+)...