In a recent post on  Venomous toxin ion channel modulators, we looked at toxin derived peptides to manipulate a wide variety of ion channels. These toxins can be used as tools to characterize specific ion channels, but they can also be utilized as reference inhibitors in ion channel drug screening campaigns.

Today, let’s take a look at cell lines over expressing specific ion channels and designed for cell based ion channel assays in drug discovery.

Ion channels are proteins with pore-forming abilities. Their selective capabilities to let ions cross the cell membrane involves them in crucial cellular functions (controlling membrance potential, the flow of ions, regulating cell volume). Ion channels are involved in the patho-physiology of so many diseases, they are natural candidates for pharma R&D programs. We will review here a series of highly selective ion channel modulators which are ideal for performing drug discovery screenings.

Acid-Sensing Ion Channels (ASICs) are neuronal voltage-insensitive cationic channels which are activated by extracellular protons. They belong to the ENaC/Deg superfamily of ion channels. Up to now 6 members of the ASIC family have been identified: ASIC1 – ASIC 4, and the splice variants ASIC1a, 1b and 2a, 2b. The ASIC family members are trimeric and can be made up of different combinations of subunits. All ASICs are expressed in the peripheral nervous system. ASIC1a, 2a, 2b and 4 are expressed in the central nervous system. ASICs are promising drug targets for treating a wide variety of conditions linked to both the CNS and PNS especially implied in pain pathways.

Fig. 1: Structure of a mono-nucleosome.

Nucleosomes are basis units of DNA packaging in eukaryotic cells. A core particle (mono-nucleosome) consists of a segment of DNA called core DNA (147 bp in length) wound around a histone octamer (Fig 1.). Histone octamers are made up of 2 copies of the the core histones H2A, H2B, H3, and H4. These mono-nucleosomes are connected by linker 80bp-long DNA. H1 histone, the so-called linker histone, binds to the linker DNA close to the entry and exit of the core DNA and is involved in chromatin compaction (Fig 1.).