Transmembrane Determinants of Voltage Gating Differences Between BK (Slo1) and Slo3 Channels

This study investigates the molecular determinants that differentiate the voltage-gating properties of human Slo1 and mouse Slo3 channels. Utilizing Slo1/Slo3 chimeras, we pinpointed the selectivity filter region as a key factor in the Slo3 channel's reduced conductance at negative voltages. The S6 transmembrane (TM) segment was identified as pivotal for the Slo3 channel's biphasic deactivation kinetics at these voltages. Additionally, the S4 and S6 TM segments were found to be responsible for the gradual slope in the Slo3 channel's conductance-voltage (G-V) relationship, while multiple TM regions appear to be involved in the Slo3 channel's requirement of strong depolarization for activation. Mutations in the Slo1's S5 and S6 TM segments revealed three residues (I233, L302, and M304) that likely play a crucial role in the allosteric coupling between the voltage sensors and the pore gate.PMID:38637987 | DOI:10.1016/j.bpj.2024.04.016

Source: Biophysical Journal - April 19, 2024 Category: Physics Authors: Qin Li Guanxing Chen Jiusheng Yan Source Type: research