Voltage Profile along the Permeation Pathway of an Open Channel

Molecular Neurophysiology Section, Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
Biophysical Journal (Impact Factor: 3.97). 11/2010; 99(9):2863-9. DOI: 10.1016/j.bpj.2010.08.053
Source: PubMed


For ion channels, the transmembrane potential plays a critical role by acting as a driving force for permeant ions. At the microscopic level, the transmembrane potential is thought to decay nonlinearly across the ion permeation pathway because of the irregular three-dimensional shape of the channel's pore. By taking advantage of the current structural and functional understanding of cyclic nucleotide-gated channels, in this study we experimentally explore the transmembrane potential's distribution across the open pore. As a readout for the voltage drop, we engineered cysteine residues along the selectivity filter and scanned the sensitivity of their modification rates by Ag(+) to the transmembrane potential. The experimental data, which indicate that the majority of the electric field drops across the selectivity filter, are in good agreement with continuum electrostatic calculations using a homology model of an open CNG channel. By focusing the transmembrane potential across the selectivity filter, the electromotive driving force is coupled with the movement of permeant ions in the filter, maximizing the efficiency of this process.

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Available from: Jorge E Contreras, Oct 07, 2015
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    • " the voltage - dependent concentration of H + within the electrical field alone , without the necessity of taking explicitly into account a voltage - dependent conformational change . The fraction of the membrane voltage at the binding site thus obtained ( δ ß0 . 37 ) is consistent with the expected location of Glu363 within the electrical field ( Contreras et al . 2010 ) . This scheme , however , appears to be critically deficient in reproducing the instantaneous and steady - state I – V relationship ( Figs 5C and 6B , blue lines ) . The basis of this shortcoming is the different pH dependency of proton blockage and inactivation . Indeed , proton blockage has been associated with an apparent acidic di"
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