Studying Ion Channels Using Marine Natural Products
Ion channels are proteins that are found in the cell membrane and allow the movement of ions across the membrane. They shape the physiological properties of different cell types. For example/they control the release of cytokines by immune cells/control the bioelectrical signals in neurons and cardiomyocytes which are important for cellular communication and proper functioning of the brain and the heart. All ion channels are made of multimeric subunits that assemble together to form a pore. One of the largest and most diverse family of ion channels is the voltage-gated potassium-channel. Although there are limited number of subunits (encoded by ~70 genes)/each subunit can combine in different combinations/resulting in an enormous array of homomeric and heteromeric subytpes. An example of different K-channel subtypes formed by two subunits is shown in the figure below. The function of different K-channel heteromers have remained elusive due to the lack of selective pharmacology to discriminate between the heteromers. Our lab discovered and developed conotoxins as pharmacological tools to study the properties of different K-channels. Conotoxins are used by cone snails for predatory purposes- they paralyze their prey by targeting various ion channels and receptors. In our lab/we have extracted and purified conopeptides from the venom of different cone snail species. In this project/we will use conopeptides and other marine bioactive compounds to study the properties and functions of different voltage gated K-channels. We will use a technique called two-electrode voltage clamp to study the properties of K-channels. Students will gain an understanding of different concepts from molecular biology/bioelectricity and biophysics.