Kalicludine


Kalicludine is a blocker of the voltage-dependent potassium channel Kv1.2 found in the snakeslocks anemone Anemonia viridis, which it uses to paralyse prey.

Etymology

“Kali”, abbreviated from the Latin word “kalium”, equals potassium. “Cludine” means to block or to enclose, as it is derived from the Latin verb “cludere”.

Structure

The kalicludine isotoxins have similar molecular size and a similar biological function. They contain three amino acid residues that are important for trypsin binding: Lys-15, Ala-16, and Ile-19 in BPTI. AsKCs have a replacement at position 19, which results in less inhibitory action than BPTI.

Mode of action

Kalicludine is stored in nematocysts or located in extracellular regions. It is known to be a dual-function toxin, able to inhibit both the serine protease trypsin and the voltage-gated potassium channels Kv1.2/KCNA2. Kalicludines and dendrotoxins compete for binding to these Kv channels.
The kalicludine sequence is homologous to the sequence of dendrotoxins, in particular DTX 1, potent blockers of Kv channels. Kalicludines have from 38 to 42% homologies with DTX. Both kalicludines and dendrotoxins increase the release of acetylcholine and enhance the duration of action potentials.

Toxicity and symptoms

Kv channel blocking dendrotoxins, and thus possibly also kalicludines, often lead to overstimulation of the cholinergic system, and subsequently to neuromuscular block and cardiovascular depression.