Gating current noise produced by Brownian models of a voltage sensor

Catacuzzeno, Luigi; Franciolini, Fabio; Bezanilla, Francisco; Eisenberg, Robert S.

doi:10.1016/j.bpj.2021.08.015

Cited by 8 publications

(14 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…6). The simulated gating currents obtained with our Brownian model reproduced all the main features of the gating currents recorded from typical K + channels (Catacuzzeno, Franciolini et al., 2021; Catacuzzeno, Sforna et al., 2021; Fig. 6).…”

Section: Introductionsupporting

confidence: 64%

“…This is crucial for reinterpreting the classical experimental data on gating current noise that indicated shot current charge packages of ∼2.3e 0 (Conti & Stühmer, 1989; Sigg et al, 1994), when recent gating models consistently suggest charge packages of 1.0e 0 . Our Brownian model has helped to resolve the conflict by showing that the relatively high charge shot deduced from the fluctuation analysis of experimental results from the limited recording bandwidth that makes the sequential gating charges crossing the gating pore in rapid succession to become indistinguishable individually, and thus appear as a single larger charge (Catacuzzeno, Franciolini et al., 2021; see also Crouzy & Sigworth, 1993).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The 70‐year search for the voltage‐sensing mechanism of ion channels

Catacuzzeno

Franciolini

2022

The Journal of Physiology

Self Cite

View full text Add to dashboard Cite

This retrospective on the voltage‐sensing mechanisms and gating models of ion channels begins in 1952 with the charged gating particles postulated by Hodgkin and Huxley, viewed as charges moving across the membrane and controlling its permeability to Na+ and K+ ions. Hodgkin and Huxley postulated that their movement should generate small and fast capacitive currents, which were recorded 20 years later as gating currents. In the early 1980s, several voltage‐dependent channels were cloned and found to share a common architecture: four homologous domains or subunits, each displaying six transmembrane α‐helical segments, with the fourth segment (S4) displaying four to seven positive charges invariably separated by two non‐charged residues. This immediately suggested that this segment was serving as the voltage sensor of the channel (the molecular counterpart of the charged gating particle postulated by Hodgkin and Huxley) and led to the development of the sliding helix model. Twenty years later, the X‐ray crystallographic structures of many voltage‐dependent channels allowed investigation of their gating by molecular dynamics. Further understanding of how channels gate will benefit greatly from the acquisition of high‐resolution structures of each of their relevant functional or structural states. This will allow the application of molecular dynamics and other approaches. It will also be key to investigate the energetics of channel gating, permitting an understanding of the physical and molecular determinants of gating. The use of multiscale hierarchical approaches might finally prove to be a rewarding strategy to overcome the limits of the various single approaches to the study of channel gating.

show abstract

Section: Introductionsupporting

confidence: 64%

Section: Introductionmentioning

confidence: 99%

The 70‐year search for the voltage‐sensing mechanism of ion channels

Catacuzzeno

Franciolini

2022

The Journal of Physiology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Though non-stationary noise analysis of ion channel gating (displacement) currents have been made and modelled [see (Catacuzzeno et al, 2021)], to our knowledge stationary noise analysis of voltage-sensor activity has not been attempted; indeed, confounding noise sources, e.g. 1/f noise, have dissuaded such attempts (Luigi Catacuzzeno, Pancho Bezanilla, personal communications).…”

Section: Resultsmentioning

confidence: 99%

Ultrasonic measures of prestin (SLC26a5) charge movements in membrane patches

Santos‐Sacchi

Bai

Navaratnam

2022

Preprint

View full text Add to dashboard Cite

Charged moieties in the outer hair cell (OHC) molecular motor protein, prestin, are driven by transmembrane voltage to ultimately provide for cochlear amplification. The speed of voltage-dependent conformational switching underlies its ability to influence micromechanics of the cell and the organ of Corti. Corresponding voltage-sensor charge movements in prestin, classically assessed as a voltage-dependent, nonlinear membrane capacitance (NLC), have been used to gauge its frequency response. Using megahertz sampling of prestin charge movements, we extend interrogations of prestin performance into the ultrasonic range (up to 120 kHz) and find response magnitude larger than previously reported. We also confirm kinetic model predictions of prestin by directly observing its cut-off frequency under voltage-clamp as the intersection frequency (Fis) of the real and imaginary components of complex NLC (cNLC), showing values near 19 kHz. At higher frequencies, the imaginary component roll-off exactly tracks that of Abs(cNLC). The frequency response of prestin displacement current noise determined from the Nyquist relation aligns with this cut-off. On the other hand, previous measures of stationary thermal-driven noise of prestin indicated that the cut-off was several fold greater than that of NLC, in violation of the fluctuation-dissipation theorem. We have attempted to confirm this apparent paradox, but find that low frequency (<10kHz), voltage-dependent 1/f noise, likely due to intrinsic prestin conductance, can limit the accessible bandwidth for stationary noise analysis. Nevertheless, within those bandwidths, frequency response comparisons of stationary measures and Nyquist relation measures are consistent. We conclude that voltage stimulation accurately assesses the spectral limits of prestin activity.

show abstract

“…The key is to always make models of specific systems-including the apparatus and setup used to study them-and then to solve those models with systematic well defined approximations that other scientists and mathematicians can verify, falsify, correct, and extend. With modern numerical and computational methods, and highly skilled mathematicians interested in these issues [187], systems as small as the voltage sensor component [188] of the protein of an ion channel [189][190][191][192][193][194][195], or as complex as the lens of the eye [196], a piece of the 'brain' (central nervous systems) [197,198], or systems that extend from the atomic to the macroscopic scale, like the cytochrome c oxidase enzyme of mitochondria [199] can be analyzed, although each involves many (sometimes 21) partial differential equations.…”

Section: Discussionmentioning

confidence: 99%

Setting Boundaries for Statistical Mechanics

Eisenberg

2022

Molecules

View full text Add to dashboard Cite

Statistical mechanics has grown without bounds in space. Statistical mechanics of noninteracting point particles in an unbounded perfect gas is widely used to describe liquids like concentrated salt solutions of life and electrochemical technology, including batteries. Liquids are filled with interacting molecules. A perfect gas is a poor model of a liquid. Statistical mechanics without spatial bounds is impossible as well as imperfect, if molecules interact as charged particles, as nearly all atoms do. The behavior of charged particles is not defined until boundary structures and values are defined because charges are governed by Maxwell’s partial differential equations. Partial differential equations require boundary structures and conditions. Boundary conditions cannot be defined uniquely ‘at infinity’ because the limiting process that defines ‘infinity’ includes such a wide variety of structures and behaviors, from elongated ellipses to circles, from light waves that never decay, to dipolar fields that decay steeply, to Coulomb fields that hardly decay at all. Boundaries and boundary conditions needed to describe matter are not prominent in classical statistical mechanics. Statistical mechanics of bounded systems is described in the EnVarA system of variational mechanics developed by Chun Liu, more than anyone else. EnVarA treatment does not yet include Maxwell equations.

show abstract

Gating current noise produced by Brownian models of a voltage sensor

Cited by 8 publications

References 38 publications

The 70‐year search for the voltage‐sensing mechanism of ion channels

The 70‐year search for the voltage‐sensing mechanism of ion channels

Ultrasonic measures of prestin (SLC26a5) charge movements in membrane patches

Setting Boundaries for Statistical Mechanics

Contact Info

Product

Resources

About