µ-TRTX-Df1a

Electrophysiology

NaV channels and T-type Ca2+ channels

The product is shipped as a lyophilized powder at room temperature. Upon receipt, store the product at -20°C. Protect from moisture.

4078.6 Da

A Blocker of Voltage-Gated Na+ and T-Type Ca2+ Channels

Centrifuge the vial (10, 000 × g for 5 minutes) before adding solvent to spin down all the powder to the bottom of the vial. The lyophilized product may be difficult to visualize. Add solvent directly to the centrifuged vial. Gently tap, tilt, and roll the vial to aid dissolution. Avoid vigorous vortexing; light vortexing for up to 3 seconds is acceptable if needed. The product is soluble in pure water at high micromolar concentrations (100 µM - 1 mM). For long-term storage in solution, we recommend preparing a stock solution by dissolving the product in double-distilled water (ddH2O) at a concentration between 100-1000x of the final working concentration. Divide the stock solution into small aliquots and store at -20°C. Before use, thaw the relevant vial(s) and dilute to the desired working concentration in your working buffer. Centrifuge all product preparations before use. It is recommended to prepare fresh solutions in working buffers just before use. Avoid multiple freeze-thaw cycles to maintain biological activity.

12352202

Disulfide bonds location- Cys2-Cys16, Cys9-Cys21, Cys15-Cys28 Phe34 - C-terminal amidation

Df1a exhibits a rank order of potency for hNaV channels as follows: 1.7 > 1.2 > 1.3 > 1.6 > 1.1 > 1.4 > 1.5, and for hCaV3 channels, the order is 3.1 > 3.3 > 3.2. Also, Df1a demonstrates a dual modulatory effect by simultaneously inhibiting peak current and slowing fast inactivation of NaV1.1, NaV1.3, and NaV1.5 subtypes1.

No

µ-TRTX-Df1a (Df1a) is a 34-amino acid peptide toxin originally isolated from the venom of the tarantula Davus fasciatus. This toxin has been identified as a potent blocker of voltage-gated sodium (NaV) and calcium (CaV)3 channels1. Df1a exhibits a rank order of potency for hNaV channels as follows: 1.7 > 1.2 > 1.3 > 1.6 > 1.1 > 1.4 > 1.5, and for hCaV3 channels, the order is 3.1 > 3.3 > 3.2. Additionally, Df1a demonstrates a dual modulatory effect by simultaneously inhibiting peak current and slowing fast inactivation of NaV1.1, NaV1.3, and NaV1.5 subtypes. It also alters the voltage dependence of activation and inactivation for most NaV subtypes1. Df1a belongs to the Family 2 of NaV-targeting spider toxins (NaSpTx), characterized by an inhibitor cystine knot (ICK) motif and highly conserved N- and C-terminal regions1. ICK peptides possess a disulfide-rich structural framework that creates a "knot, " imparting exceptional structural, thermal, and proteolytic stability. CaV3 are T-type, low voltage-gated calcium channels. Their electrophysiological properties include low voltage thresholds for activation and inactivation, rapid inactivation, and rebound bursting. These properties are responsible for the CaV3-mediated fine-tuned regulation of neuronal excitability in both the central nervous system (CNS) and peripheral nervous system (PNS)2. Nav channels are involved in a wide array of physiological processes. There are nine mammalian subtypes of voltage-gated sodium (NaV) channels: NaV1.1–NaV1.9. They are transmembrane proteins responsible for propagating action potentials in excitable cells, most notably nerves and muscle. These channels are considered to be important therapeutic targets for a wide variety of pathophysiological conditions such as chronic pain, cardiac arrhythmia, and epilepsy3, 4. Df1a acted as an analgesic in vivo, alleviating the spontaneous pain behaviors triggered by the NaV activator OD11.