Eduardo M Salinas-Stefanon

• MD, PhD
• Principal Investigator at Meritorious Autonomous University of Puebla

Cannabinoids regulate analgesia, which has aroused much interest in identifying new pharmacological therapies in the management of refractory pain. Voltage-gated Na+ channels (Navs) play an important role in inflammatory and neuropathic pain. In particular, Nav1.9 is involved in nociception and the understanding of its pharmacology has lagged behin...

(1) Background: voltage-gated sodium channels (Navs) are integral membrane proteins that allow the sodium ion flux into the excitable cells and initiate the action potential. They comprise an α (Navα) subunit that forms the channel pore and are coupled to one or more auxiliary β (Navβ) subunits that modulate the gating to a variable extent. (2) Met...

Mefloquine constitutes a multitarget antimalaric that inhibits cation currents. However, the effect and the binding site of this compound on Na⁺ channels is unknown. To address the mechanism of action of mefloquine, we employed two-electrode voltage clamp recordings on Xenopus laevis oocytes, site-directed mutagenesis of the rat Na⁺ channel, and a...

The mechanism of inactivation of mammalian voltage-gated Na(+) channels involves transient interactions between intracellular domains resulting in direct pore occlusion by the IFM motif and concomitant extracellular interactions with the β1 subunit. Navβ1 subunits constitute single-pass transmembrane proteins that form protein-protein associations...

The molecular structure modeling of the β1 subunit of the skeletal muscle voltage-gated sodium channel (Nav1.4) was carried out in the twilight zone of very low homology. Structural significance can per se be confounded with random sequence similarities. Hence, we combined (i) not automated computational modeling of weakly homologous 3D templates,...

Voltage-gated sodium channels (VGSCs) are heteromeric protein complexes that initiate action potentials in excitable cells. The voltage-gated sodium channel accessory subunit, Navβ1, allosterically modulates the α subunit pore structure upon binding. To date, the molecular determinants of the interface remain unknown. We made use of sequence, knowl...

The aim of our computed study was to examine the possible binding site of primaquine (PQ) using a combined homology protein modeling, automated docking, and experimental approach. The target models of wild type and mutant types of the voltagedependent sodium channel in rat skeletal muscle (rNav 1.4) were based on previous work by other researchers....

Our study on the wild-type and mutants of the voltage-dependent sodium channel in the rat skeletal muscle Na(v) 1.4 was to examine the possible binding site of primaquine PQ by using an experimental approach. We used a standard voltage-clamp in oocytes. Previously, we had demonstrated that PQ blocks the voltage-dependent sodium current in rat myocy...

Thomas RF Scior1, Evelyn Martínez-Morales2, Silvia L Cruz3, Eduardo M Salinas-Stefanon21Departamento de Farmacia; 2Instituto de Fisiología, Benemérita Universidad Autónoma de Puebla, Ciudad Universitaria, Puebla, Pue, México; 3Departamento de Farmacobiología, CINVESTAV-IPN, Calz. Col. Granjas Coapa, MéxicoAbstract: Toluene is a commonly used organi...

Chlorthalidone is used for the treatment of hypertension as it produces a lengthening of the cardiac action potential. However, there is no experimental evidence that chlorthalidone has electrophysiological effects on the potassium currents involved in cardiac repolarization. Ventricular myocytes and oocytes, transfected with human ionic channels t...

Toluene is a solvent of abuse that inhibits cardiac sodium channels in a manner that resembles the action of local anaesthetics. The purpose of this work was to analyze toluene effects on skeletal muscle sodium channels with and without beta1 subunit (Nav1.4+beta1 and Nav1.4-beta1, respectively) expressed in Xenopus laevis oocytes and to compare th...

To determine the characteristics of a TTX-sensitive Ca(2+) current that occurred only following remodelling after myocardial infarction in Wistar rat. Using the whole-cell patch-clamp technique, we studied ionic inward current in myocytes isolated from four different ventricular regions of control Wistar rat hearts, or from hearts 4 to 6 months aft...

Toluene is an industrial solvent widely used as a drug of abuse, which can produce sudden sniffing death due to cardiac arrhythmias. In this paper, we tested the hypothesis that toluene inhibits cardiac sodium channels in Xenopus laevis oocytes transfected with Na v 1.5 cDNA and in isolated rat ventricular myocytes. In oocytes, toluene inhibited so...

The electrophysiological effects of the anti-malarial drug primaquine on cardiac Na+ channels were examined in isolated rat ventricular muscle and myocytes. In isolated ventricular muscle, primaquine produced a dose-dependent and reversible depression of dV/dt during the upstroke of the action potential. In ventricular myocytes, primaquine blocked...

The effects of the antimalarial drug chloroquine on cardiac action potential and membrane currents were studied at clinically relevant concentrations. In cat Purkinje fibers, chloroquine at concentrations of 0.3 to 10 microM increased action potential duration, and reduced maximum upstroke velocity. At concentrations of 3 and 10 microM, chloroquine...

In long term treatment, thiazide diuretics such as hydrochlorothiazide (HCTZ) lower blood pressure by decreasing peripheral resistance rather than by their diuretic effect. This action has been attributed to the opening of Ca2+-activated K+ channels in vascular smooth muscle cells. However, little is known about their cardiac cellular actions. Here...

In long term treatment, thiazide diuretics such as hydrochlorothiazide (HCTZ) lower blood pressure by decreasing peripheral resistance rather than by their diuretic effect. This action has been attributed to the opening of Ca2+-activated K+ channels in vascular smooth muscle cells. However, little is known about their cardiac cellular actions. Here...

The effects were studied of a toxin (Bainh) isolated from the secretion of the Caribbean sea anemone Bunodosoma granulifera on electrical and mechanical activities of rat ventricular muscle. The effects on the ionic currents of single rat and dog ventricular cardiomyocytes were studied using the whole-cell recording patch-clamp technique. In the co...

The effects of quinidine on calcium‐independent outward K ⁺ currents in rat ventricular myocytes were studied using whole‐cell patch clamp techniques. Quinidine sulphate (6 μ m ) significantly prolonged repolarization of the ventricular action potential. This effect was larger during early repolarization (25% level) than at later times (90% level)....

The ionic mechanisms for differences in action potential waveforms in rat left ventricle were studied by recording L-type Ca2+ current, transient outward K+ current, and inwardly rectifying background K+ current in single myocytes. Single cells were obtained from adult rat hearts by enzymatic dispersion of tissue segments from the epicardium at the...