A Novel Insecticidal Spider Peptide that Affects the Mammalian Voltage-Gated Ion Channel hKv1.5

Spider venoms include various peptide toxins that modify the ion currents, mainly of excitable insect cells. Consequently, scientific research on spider venoms has revealed a broad range of peptide toxins with different pharmacological properties, even for mammal species. In this work, thirty animal venoms were screened against hKv1.5, a potential target for atrial fibrillation therapy. The whole venom of the spider Oculicosa supermirabilis, which is also insecticidal to house crickets, caused voltage-gated potassium ion channel modulation in hKv1.5. Therefore, a peptide from the spider O. supermirabilis venom, named Osu1, was identified through HPLC reverse-phase fractionation. Osu1 displayed similar biological properties as the whole venom; so, the primary sequence of Osu1 was elucidated by both of N-terminal degradation and endoproteolytic cleavage. Based on its primary structure, a gene that codifies for Osu1 was constructed de novo from protein to DNA by reverse translation. A recombinant Osu1 was expressed using a pQE30 vector inside the E. coli SHuffle expression system. recombinant Osu1 had voltage-gated potassium ion channel modulation of human hKv1.5, and it was also as insecticidal as the native toxin. Due to its novel primary structure, and hypothesized disulfide pairing motif, Osu1 may represent a new family of spider toxins.

Age-related hearing loss pertaining to potassium ion channels in the cochlea and auditory pathway

Age-related hearing loss (ARHL) is the most prevalent sensory deficit in the elderly and constitutes the third highest risk factor for dementia. Lifetime noise exposure, genetic predispositions for degeneration, and metabolic stress are assumed to be the major causes of ARHL. Both noise-induced and hereditary progressive hearing have been linked to decreased cell surface expression and impaired conductance of the potassium ion channel KV7.4 (KCNQ4) in outer hair cells, inspiring future therapies to maintain or prevent the decline of potassium ion channel surface expression to reduce ARHL. In concert with KV7.4 in outer hair cells, KV7.1 (KCNQ1) in the stria vascularis, calcium-activated potassium channels BK (KCNMA1) and SK2 (KCNN2) in hair cells and efferent fiber synapses, and KV3.1 (KCNC1) in the spiral ganglia and ascending auditory circuits share an upregulated expression or subcellular targeting during final differentiation at hearing onset. They also share a distinctive fragility for noise exposure and age-dependent shortfalls in energy supply required for sustained surface expression. Here, we review and discuss the possible contribution of select potassium ion channels in the cochlea and auditory pathway to ARHL. We postulate genes, proteins, or modulators that contribute to sustained ion currents or proper surface expressions of potassium channels under challenging conditions as key for future therapies of ARHL.

Mutations in genes associated with inherited arrhythmias in patients with Brugada syndrome

Методом высокопроизводительного секвенирования у пациентов с синдромом Бругада проведен поиск мутаций в генах, ассоциированных с наследственными аритмиями. Половина нуклеотидных замен локализована в генах, кодирующих белки натриевых и калиевых ионных каналов (SCN5A, KCNJ2, KCNJ8, HCN4, KCNQ1). Выявлены мутации в генах, ассоциированных преимущественно с другими каналопатиями и аритмогенными кардиомиопатиями. Mutation detection in the coding sequences of genes associated with inherited arrhythmias was performed by next generation sequencing (NGS) in patients with Brugada syndrome. Half of the mutations are located in the genes encoding the sodium and potassium ion channel proteins (SCN5A, KCNJ2, KCNJ8, HCN4, KCNQ1). In the genes associated predominantly with other canalopathies and arrhythmogenic cardiomyopathies the mutations were found.

Variation of the Spiking Dynamics of a Hodgkin-Huxley Neuron with an Electrical Autaptic Connection Under Ion Channel Blocking

In this paper, we investigate how the blockage of potassium and sodium ion channels embedded in membranes affects the spiking dynamics of a Hodgkin-Huxley neuron model owing autaptic connection. We consider an electrical autapse expressed by its coupling strength and delay time. It is found that the spiking behavior of the neuron becomes more ordered with the increment of autaptic conductance regardless of the ion channel block level. Furthermore, it is obtained that the blockage of potassium and sodium ion channels influences differently to the spiking regularity of the neuron. Potassium ion channel blockage promotes regularity, whereas sodium ion channel blockage destroys.