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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 Nav1.2? and Nav1.2 (? + ?1) 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 ?-like toxins such as BmK AS modulate gating properties and peak currents of VGSCs.

SUBMITTER: Liu ZR

PROVIDER: S-EPMC5379197 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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PKA phosphorylation reshapes the pharmacological kinetics of BmK AS, a unique site-4 sodium channel-specific modulator.

Liu Z R ZR Zhang H H Wu J Q JQ Zhou J J JJ Ji Y H YH

Scientific reports 20140116

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 a ...[more]

PMID: 24430351

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