Analysis Biomolecular Interactions of the Sodium and Calcium Ion Channel with Neurotoxins in Helodermatid and Varanid Lizard Venoms by BLI (CAT#: STEM-MB-0118-CJ)

Introduction

Voltage-gated ion channels allow the movement of ions across cellular membranes, regulating resting and action potentials. Depending on the type of ions transported, they are categorized as voltage-gated sodium (NaV), calcium (CaV), potassium (KV), or chloride channels (CLC).

Due to common evolutionary origin, NaV, CaV and KV channels share architectural similarities. Their α-subunits are comprised of four identical or homologous domains each, with associated voltage-sensing domains (I-IV). Each domain consists of six transmembrane segments (S1–S6). In NaV channels, voltage-sensing domains I–III are important in channel opening while voltage-sensing domain IV is involved in gating regulation and the fast termination of ion flux post-activation. Similarly, in CaV gating, voltage-sensing domains II and III make a major contribution to channel activation, while voltage-sensing domain I are thought to have a minor role in activation. The ion channel-binding toxins can lead to an increase in, or inhibition of, the release of the cholinergic neurotransmitter acetylcholine. Toxins that bind to this locus in voltage-sensing domains I–III typically inhibit channel opening, while toxins that exclusively target voltage-sensing domain IV delay fast inactivation, resulting in spastic paralysis, such as that of the elapid snake Calliophis bivirgatus. A toxin isolated from the tarantula Hysterocrates gigas interacts with voltage-sensing domains III and IV to inhibit CaV channel gating. Similarly, ProTx-II from the tarantula Thrixopela pruriens inhibits NaV channel gating via voltage-sensing domains II and IV binding, which may cause flaccid paralysis.