Chinese spider toxin activates and inhibits sodium channels
Voltage-gated sodium channels (Nav) play a central role in generating and transmitting nerve signals. In humans, there are nine Nav subtypes (Nav1.1 to Nav1.9) which, to a large extent, share amino acid sequences but localize differently, suggesting specialized functions.
The first member of the Nav family, Nav1.1, is predominantly expressed in inhibitory neurons, tuning down neuronal network excitability. Loss-of-function mutations in Nav1.1 cause Dravet syndrome, characterized by early-onset seizures and cognitive impairment. Therefore, Nav1.1 is now considered an important pharmacological target for treating Dravet syndrome, and so, identifying new activating agents for this channel is an essential endeavor.
In a recent study by Lopez et al., the Chinese tarantula peptide, JzTx-34, has been (re)discovered as an activator of the human Nav1.1 channel. Using an automated patch clamp system, SyncroPatch 384, the authors demonstrated that JzTx-34 significantly slows down the fast inactivation of hNav1.1, promoting a large sustained current. Interestingly, JzTx-34 also activated hNav1.3 and hNav1.6 channels, while blocking hNav1.2, Nav1.5, and Nav1.7 channels.
In this regard, JzTx-34 represents a remarkable model peptide for understanding the molecular basis of channel-peptide interactions, as it has the capability to act both as an inhibitor and an activator.
Congratulations to all the authors on this great paper, and we are looking forward to new discoveries.
For more details, please refer to the paper here: https://www.sciencedirect.com/science/article/pii/S0753332223009642
Learn more about the SyncroPatch 384, a revolutionary automated patch clamp system combining high quality electrophysiological data acquisition and analysis with state-of-the-art liquid handling: https://www.nanion.de/products/syncropatch-384/