TY - JOUR TI - Unmasking coupling between channel gating and ion permeation in the muscle nicotinic receptor AU - Strikwerda, John R AU - Sine, Steven M A2 - Swartz, Kenton J A2 - Goldschen-Ohm, Marcel P A2 - Goldschen-Ohm, Marcel P A2 - Sigworth, Fred A2 - Keramidas, Angelo VL - 10 PY - 2021 DA - 2021/04/06 SP - e66225 C1 - eLife 2021;10:e66225 DO - 10.7554/eLife.66225 UR - https://doi.org/10.7554/eLife.66225 AB - Whether ion channel gating is independent of ion permeation has been an enduring, unresolved question. Here, applying single channel recording to the archetypal muscle nicotinic receptor, we unmask coupling between channel gating and ion permeation by structural perturbation of a conserved intramembrane salt bridge. A charge-neutralizing mutation suppresses channel gating, reduces unitary current amplitude, and increases fluctuations of the open channel current. Power spectra of the current fluctuations exhibit low- and high-frequency Lorentzian components, which increase in charge-neutralized mutant receptors. After aligning channel openings and closings at the time of transition, the average unitary current exhibits asymmetric relaxations just after channel opening and before channel closing. A theory in which structural motions contribute jointly to channel gating and ion conduction describes both the power spectrum and the current relaxations. Coupling manifests as a transient increase in the open channel current upon channel opening and a decrease upon channel closing. KW - ligand gated ion channels KW - single channel recording KW - open channel fluctuations JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -