Computational biophysicists are not used to making discoveries, says Jianhan Chen, Professor of Chemistry and Biochemistry & Molecular Biology, so when he and colleagues cracked the secret of how cells regulate Big Potassium (BK) channels, they thought it must be a computational artifact. But after many simulations and tests, they convinced themselves that they have identified the BK gating mechanism that had eluded science for many years.
BK channels are important in neuronal and muscle functions and are associated with pathogenesis of hypertension, autism, epilepsy, stoke, asthma, etc. A key puzzle has been trying to understand how cells close, or gate, BK channels, which have an unusually large central pore. “There were a lot of hypotheses, but no answers,” Chen notes. Now in Nature Communications, his team demonstrates that a phenomenon known as “hydrophobic dewetting” gives rise to a vapor phase in the pore’s central cavity to block intracellular access to the selectivity filter.
Chen’s work on BK channels has also led to a new four-year, $2.9 million grant from NIH’s National Heart, Lung, and Blood Institute. The collaborative team includes Jianmin Cui at Washington University, St. Louis, Chen at UMass Amherst and Xiaoqin Zou at the University of Missouri.