Voltage-gated ion channels are transmembrane proteins that selectively
permeate K+, Na+, or Ca2+ in response to the plasma membrane voltage changes. They
play an essential role in neuronal excitability and molecular signaling in central and
peripheral nervous systems. Dysfunctions of these ion channels are involved in various
neurological disorders such as pain, migraine, schizophrenia, Alzheimer's disease,
epilepsy, depression, etc. Thus, increasing numbers of academic and medical
institutions and pharmaceutical industries have paid attention to these ion channel
proteins as therapeutic targets. Consequently, a number of medicines modulating the
channel functions have been being developed. Among the voltage-gated ion channel
modulators, peptide neurotoxins from venomous animals such as cone snails, spiders,
scorpions, and sea anemones are noticeable in that they modify voltage-gated ion
channel activities in highly selective and potent manners. The distinctive selectivity and
potency are based on their particularly rigid three-dimensional structures with multiple
disulfide bonds, which confer strong and specific binding to a channel subtype. Varied
inter-cysteine sequences further give an additional specificity. Ziconotide, blocking
neuronal N-type voltage-gated Ca2+ channels in this mechanism, is the first FDAapproved
peptide toxin for neurological diseases. Several other peptidergic neurotoxins
are in preclinical or clinical phases. Here, we update knowledge on molecular and
functional characteristics of the peptide neurotoxins targeting voltage-gated ion
channels in the nervous system. We also discuss their current status of research and
developments and their future therapeutic potentials.
Keywords: Peptide neurotoxin, voltage-gated K+ channels, voltage-gated Na+
channels, voltage-gated Ca2+ channels, Neurological diseases, molecular
properties, therapeutic potentials.
