Small molecule regulation of SK channels

Small conductance Ca2+-activated K+ (SK) channels are a small family of ion-gated K+ channels involved in synaptic plasticity, which is a key process in learning and memory. These channels are controlled primarily by changes in the concentration of intracellular calcium through opening and closing of N-type calcium channels. Ca2+ bound to calmodulin directly binds the C-terminus of the channel, changing its conformation. SK channels can be found throughout the central nervous system where they manage neuronal action potential discharge frequency.

Recently, an article published in Science Advances highlights the role of phosphatidylinositol 4,5-bisphosphate (PIP2) as a modulator of SK channel activity. PIP2 is a known cofactor involved in regulation of many ion channels, although its role in respect to SK channels had previously been undetermined. In this study, scientists used SK channel inhibitors to examine the role of PIP2. Results indicated that PIP2 chaperones the binding of the Ca2+-calmodulin complex to the channel, facilitating channel opening and closing.

This study highlights the role of PIP2 in SK channel regulation, suggesting a new target – that of the PIP2-SK channel interaction – in the development of new SK channel activators and blockers, compounds that may show benefit in the treatment of neurodegenerative diseases and substance abuse disorders.

For more information on the original study, click here.

LKT carries several compounds that modulate SK channel activity! Click the representative links below for more information.

• A6002 Apamin
• B8261 Bupivacaine