UB Paderborn / Katalog / Suche / Details

Ergebnis 2 von 303291

Biochemical and biophysical research communications, 2020-12, Vol.533 (4), p.958-964

2020

Autor(en) / Beteiligte

Titel

Recombinant PaurTx-3, a spider toxin, inhibits sodium channels and decreases membrane excitability in DRG neurons

Ist Teil von

Biochemical and biophysical research communications, 2020-12, Vol.533 (4), p.958-964

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2020

Link zum Volltext

Quelle

Elsevier ScienceDirect Journals Complete

Beschreibungen/Notizen

Voltage-gated sodium channels are critical for the generation and propagation of action potentials. Gating modifier toxins from spider venom can modulate the gating mechanism of sodium channels and thus have potential as drug leads. Here, we established expression of the gating modifier toxin PaurTx-3, a sodium channel inhibitor found in the venom of the spider Phrixotrichus auratus. Whole-cell voltage-clamp recordings indicated that recombinant PaurTx-3 (rPaurTx-3) inhibited Nav1.4, Nav1.5, and Nav1.7 currents with IC50 values of 61 nM, 72 nM, and 25 nM, respectively. Furthermore, rPaurTx-3 irreversibly inhibited Nav1.7 currents, but had 60–70% recovery in Nav1.4 and Nav1.5 after washing with a bath solution. rPaurTx-3 also hyperpolarized the voltage-dependent steady-state inactivation curve and significantly slowed recovery from fast inactivation of Nav1.7. Current-clamp recordings showed that rPaurTx-3 suppressed small DRG neuron activity. The biological activity assay findings for rPaurTx-3 support its potent pharmacological effect in Nav1.7 and small DRG neurons. •Spider peptide toxin PaurTx-3 is successfully obtained by recombinant expression.•rPaurTx-3 shows high affinity against Nav1.7 channel.•rPaurTx-3 inhibits the excitability of small mouse DRG neurons.

Sprache: Englisch
Identifikatoren: ISSN: 0006-291X
eISSN: 1090-2104
DOI: 10.1016/j.bbrc.2020.09.103
Titel-ID: cdi_crossref_primary_10_1016_j_bbrc_2020_09_103

Format: –
Schlagworte: Action potential, Action Potentials - drug effects, Amino Acid Sequence, Animals, Arthropod Proteins - genetics, Arthropod Proteins - toxicity, Ganglia, Spinal - cytology, Ganglia, Spinal - drug effects, Ganglia, Spinal - metabolism, HEK293 Cells, Humans, Ion Channel Gating - drug effects, Mice, Mice, Inbred ICR, Muscle Proteins - antagonists & inhibitors, Muscle Proteins - genetics, Muscle Proteins - metabolism, NAV1.5 Voltage-Gated Sodium Channel - drug effects, NAV1.5 Voltage-Gated Sodium Channel - genetics, NAV1.5 Voltage-Gated Sodium Channel - metabolism, Nav1.7, NAV1.7 Voltage-Gated Sodium Channel - drug effects, NAV1.7 Voltage-Gated Sodium Channel - genetics, NAV1.7 Voltage-Gated Sodium Channel - metabolism, Patch-Clamp Techniques, Rats, Recombinant expression, Recombinant Proteins - genetics, Recombinant Proteins - toxicity, Sensory Receptor Cells - drug effects, Sensory Receptor Cells - metabolism, Sequence Alignment, Sodium channel, Sodium Channels - genetics, Sodium Channels - metabolism, Spider peptide toxin PaurTx-3, Spider Venoms - genetics, Spider Venoms - toxicity, Voltage-Gated Sodium Channel Blockers - toxicity, Voltage-Gated Sodium Channels - drug effects, Voltage-Gated Sodium Channels - genetics, Voltage-Gated Sodium Channels - metabolism

Empfehlungen zum selben Thema automatisch vorgeschlagen von bX