Analysis of patchclamp recordings: model-free multiscale methods and software

Florian Pein,Benjamin Eltzner,Axel Munk

doi:10.1007/s00249-021-01506-8

Abstract

Analysis of patchclamp recordings is often a challenging issue. We give practical guidance how such recordings can be analyzed using the model-free multiscale idealization methodology JSMURF, JULES, and HILDE. We provide an operational manual how to use the accompanying software available as an R-package and as a graphical user interface. This includes selection of the right approach and tuning of parameters. We also discuss advantages and disadvantages of model-free approaches in comparison to hidden Markov model approaches and explain how they complement each other.

Highlights

The patchclamp technique has been and still is a fundamental tool for the quantitative analysis of electrophysiological processes of transmembrane proteins, in particular of ion channels (Neher and Sakmann 1976; Sakmann and Neher 1995)
It shows a recording of the outer membrane porin PorB from Neisseria meningitidis, a pathogenic bacterium in the human nose and throat region (Virji 2009)
Afterwards, in “Review of existing model-free idealization approaches”, we review some existing model-free idealization methods, with a particular focus on our approaches JSMURF, JULES, and HILDE

Summary

Introduction

The patchclamp technique has been and still is a fundamental tool for the quantitative analysis of electrophysiological processes of transmembrane proteins, in particular of ion channels (Neher and Sakmann 1976; Sakmann and Neher 1995). We note that the local deconvolution approach used in our model-free idealization methods, see (Pein et al 2018), can be used to improve HMM-based idealizations, obtained, for instance, by a Viterbi algorithm, as our approach takes into account explicitly the filtering, but is time-continuous It only relies on a prior fit that fixes the number of conductance changes and their rough locations. It can be called by the function deconvolveLocally in the package clampSeg. HMM versus model-free idealization: compared and contrasted In general, HMM-based approaches achieve a higher temporal resolution of gating dynamics because of their stronger assumptions. Both approaches should be used to verify each other’s results, both in terms of parameter estimation and of idealizations

Discussion

Compliance with ethical standards