title: PKA phosphorylation reshapes the pharmacological kinetics of BmK AS, a unique site-4 sodium channel-specific modulator.
abstract: Although modulation of the activity of voltage-gated sodium channels (VGSCs) by protein kinase A (PKA) phosphorylation has been investigated in multiple preparations, the pharmacological sensitivity of VGSCs to scorpion toxins after PKA phosphorylation has rarely been approached. In this study, the effects of BmK AS, a sodium channel-specific modulator from Chinese scorpion Buthus martensi Karsch, on the voltage-dependent activation and inactivation of Nav1.2 were examined before and after PKA activation. After PKA phosphorylation, the pattern of dose-dependent modulation of BmK AS, on both Nav1.2α and Nav1.2 (α + β1) was reshaped. Meanwhile, the shifts in voltage-dependency of activation and inactivation induced by BmK AS were attenuated. The results suggested that PKA might play a role in different patterns how β-like toxins such as BmK AS modulate gating properties and peak currents of VGSCs.
authors.affiliation: 1] Department of Pharmacology, Institute of Medical Science, Shanghai Jiao Tong University School of Medicine, South Chongqing Road 280, Shanghai 200025, P.R.China [2] Lab of Neuropharmacology and Neurotoxicology, Shanghai University, Nanchen Road 333, Shanghai 200436, P.R. China.
authors.forename: Z R
authors.initials: ZR
authors.lastname: Liu
authors.affiliation: Lab of Neuropharmacology and Neurotoxicology, Shanghai University, Nanchen Road 333, Shanghai 200436, P.R. China.
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Lab of Neuropharmacology and Neurotoxicology, Shanghai University, Nanchen Road 333, Shanghai 200436, P.R. China.
authors.forename: J Q
authors.initials: JQ
authors.lastname: Wu
authors.affiliation: Lab of Neuropharmacology and Neurotoxicology, Shanghai University, Nanchen Road 333, Shanghai 200436, P.R. China.
authors.forename: J J
authors.initials: JJ
authors.lastname: Zhou
authors.affiliation: 1] Lab of Neuropharmacology and Neurotoxicology, Shanghai University, Nanchen Road 333, Shanghai 200436, P.R. China [2] Shanghai Chongmin Xinhua Translational Institute of Cancer Pain, Nanmen Road 25, Shanghai 202151, P.R. China.
authors.forename: Y H
authors.initials: YH
authors.lastname: Ji
mesh_terms: D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D007700:Kinetics; D062551:NAV1.2 Voltage-Gated Sodium Channel / Q000378:metabolism; D010455:Peptides / Q000493:pharmacokinetics*; D010766:Phosphorylation; D012604:Scorpion Venoms / Q000493:pharmacokinetics*; D012605:Scorpions / Q000737:chemistry; D013997:Time Factors
chemical_list: C119407:BmK AS polypeptide; D062551:NAV1.2 Voltage-Gated Sodium Channel; D010455:Peptides; D012604:Scorpion Venoms; D017868:Cyclic AMP-Dependent Protein Kinases