Seminarium Zakładu Biofizyki

Ion channels play a crucial role in cellular function by conducting ions across membranes. The invention of the patch-clamp technique has made it possible to study their activity at the single-molecule level. Among the evolutionary conserved classes of ion channels, those selective for potassium ions are particularly intriguing. Traditionally, potassium channels have been described as water-filled pores with physical gates that regulate ion flow. However, recent studies challenge this paradigm, showing that potassium channel pores can obstruct ion conduction without fully closing by leveraging hydrophobicity to repel water molecules.The large-conductance calcium-activated potassium (BK) channel exemplifies this mechanism. In our collaborative studies using molecular dynamics simulations and patch-clamp experiments, we demonstrated that paxilline, a high-affinity hydrophobic inhibitor of the BK channel, promotes channel pore dehydration. Furthermore, we identified two additional hydrophobic weak small-molecule inhibitors—dibenzoylmethane and chalcone—that block BK channels. These findings suggest a common inhibition mechanism based on water expulsion, opening new avenues for understanding potassium channel pharmacology.

BIO:Piotr Koprowski is a Professor at the Laboratory of Intracellular Ion Channels at the Nencki Institute of Experimental Biology PAS. He graduated from the Department of Biology at the University of Warsaw in 1997 and earned his Ph.D. in 2003 at the Institute of Biochemistry and Biophysics PAS, focusing on mitochondrial DNA repair. During this time, his interest shifted toward ion channels, leading him to investigate bacterial mechanosensitive channels at the Nencki Institute. From 2004 to 2007, he pursued postdoctoral training at the University of California, Berkeley, where he further explored mechanosensitive channels. Upon returning to the Nencki Institute, he continued his research on these channels until 2015, when his focus shifted to human potassium channels. Currently, his research is centered on the regulation and pharmacology of potassium channels, with a particular interest in their protein partners, structural dynamics, and potential therapeutic targeting.