RESUMEN
The large-conductance calcium-activated potassium (BK) channels distributed in both excitable and non-excitable cells are key participants in a variety of physiological functions. By employing numerous high-affinity natural toxins originated from scorpion venoms the pharmacological and structural characteristics of these channels tend to be approached. A 37-residue short-chain peptide, named as martentoxin, arising from the venom of the East-Asian scorpion (Buthus martensi Karsch) has been investigated with a comparatively higher preference for BK channels over other voltage-gated potassium (Kv) channels. Up to now, since the specific drug tool probing for clarifying structure-function of BK channel subtypes and related pathology remain scarce, it is of importance to illuminate the underlying mechanism of molecular interaction between martentoxin and BK channels. As for it, the current review will address the recent progress on the studies of pharmacological characterizations and molecular determinants of martentoxin targeting on BK channels.
Asunto(s)
Humanos , Secuencia de Aminoácidos , Canales de Potasio de Gran Conductancia Activados por el Calcio , Ligandos , Péptidos , Química , Venenos de Escorpión , QuímicaRESUMEN
Diverse subtypes of voltage-gated sodium channels (VGSCs) have been found throughout tissues of the brain, muscles and the heart. Neurotoxins extracted from the venom of the Asian scorpion Buthus martensi Karsch (BmK) act as sodium channel-specific modulators and have therefore been widely used to study VGSCs. α-type neurotoxins, named BmK I, BmK αIV and BmK abT, bind to receptor site-3 on VGSCs and can strongly prolong the inactivation phase of VGSCs. In contrast, β-type neurotoxins, named BmK AS, BmK AS-1, BmK IT and BmK IT2, occupy receptor site-4 on VGSCs and can suppress peak currents and hyperpolarize the activation kinetics of sodium channels. Accumulating evidence from binding assays of scorpion neurotoxins on VGSCs, however, indicate that pharmacological sensitivity of VGSC subtypes to different modulators is much more complex than that suggested by the simple α-type and β-type neurotoxin distinction. Exploring the mechanisms of possible dynamic interactions between site 3-/4-specific modulators and region- and/or species-specific subtypes of VGSCs would therefore greatly expand our understanding of the physiological and pharmacological properties of diverse VGSCs. In this review, we discuss the pharmacological and structural diversity of VGSCs as revealed by studies exploring the binding properties and cross-competitive binding of site 3- or site 4-specific modulators in VGSC subtypes in synaptosomes from distinct tissues of diverse species.
Asunto(s)
Animales , Humanos , Sitios de Unión , Unión Competitiva , Encéfalo , Metabolismo , Corazón , Fisiología , Proteínas de Insectos , Genética , Metabolismo , Insectos , Activación del Canal Iónico , Fisiología , Cinética , Mamíferos , Músculos , Metabolismo , Neurotoxinas , Química , Clasificación , Farmacología , Unión Proteica , Escorpiones , Química , Sodio , Metabolismo , Bloqueadores de los Canales de Sodio , Farmacología , Canales de Sodio , Clasificación , Genética , Metabolismo , Sinaptosomas , MetabolismoRESUMEN
<p><b>OBJECTIVE</b>To examine the effect of deglycosylation on gating properties of rNav1.3.</p><p><b>METHODS</b>rNav1.3 was expressed in Xenopus oocyte, with glycosylation inhibition by using tunicamycin. Two-electrode voltage clamp was employed to record the whole-cell sodium current and data were analyzed by Origin software. Those of glycosylated rNav1.3 were kept as control.</p><p><b>RESULTS</b>Compared with glycosylated ones, the steady-state activation curve of deglycosylated rNav1.3 was positively shifted by about 10 mV, while inactivation curve was negatively shifted by about 8 mV.</p><p><b>CONCLUSION</b>Glycosylation altered the gating properties of rNav1.3 and contributed to the functional diversity.</p>