MDC Researchers Develop New Tool to Investigate Ion Channels — Application of Neurotoxins of Cone Snails and Spiders

There are
approximately 500 species of cone snails, each producing 50 – 200 different
conotoxins. A similar number of peptide toxins are produced by snakes, spiders,
sea anemones, scorpions and other venomous animals. The animals use the
neurotoxins to paralyze their prey. 

Scientists
estimate that more than 100,000 neurotoxins exist. They have become a topic of
enormous research interest: Using neurotoxins researchers can target different
ion channels, receptors and other signaling molecules and characterize their
physiological function. 

This kind of
research can also give them insight into disease processes and eventually help
them to find new therapies to eventually block hyperactive ion channels. For
instance, a compound (Ziconotide) based on the toxin of a cone snail is already
used to treat severe chronic pain in patients. 

Dr. Ibañez-Tallon’s
research group is concentrating on two ion channels in the membrane of neurons
which are activated by electric stimulation (action potential). Once activated,
they allow the influx of calcium ions into
the neuron, and the cell then releases chemicals (neurotransmitters), which
send the signal to the next neuron. 

During
the last decades soluble neurotoxins have greatly helped in the
characterization of ion channels and receptors because of their ability to
specifically bind and inhibit these channels. However, soluble neurotoxins can only be applied for limited time, and
their activity cannot be directed to specific cells. 

Sebastian Auer, Annika S. Stürzebecher and Dr.
Ibañez-Tallon managed to circumvent this problem with genetic engineering.
Using lentiviruses they developed a shuttle to deliver the genes of cone snail
and spider toxins into the neurons. The result: The neurons now long-lastingly
produce toxins which directly bind to the calcium ion channels the researchers
want to investigate. This was the first step – the targeted and long-lasting
binding of the toxins to a specific ion channel in the cell culture. 

Secondly, the
researchers were able to demonstrate that with their tool they can also express
toxin genes in animals in a targeted way and also lastingly characterize ion channels.
In transgenic mice they were able to block certain calcium ion channels with
their toxins and thus block chronic pain. 

Neurotoxins of cone snails and spiders block neurotransmission and chronic pain (Graphics: Sebastian Auer/​Copyright: MDC)