Obtaining transition rates from single-channel data without initial parameter seeding

Abstract

Background and Purpose: Ion-channels are membrane proteins that can adopt several distinct structural conformations. Some of the conformations are open and allow the passage of ions through the membrane; others are closed and hinder ion flow. Patch-clamp recordings of single ion-channels show if a channel is open or closed, but does not immediately reveal the underlying mechanism, which typically includes several open and closed conformations. With kinetic analysis of single-channel data, sequences of observed open and closed times are fitted to proposed schemes to deduct the underlying kinetics of the ion-channel. Current programs to perform kinetic analysis uses initial parameter guessing. Here an alternative approach that uses a global fitting procedure and no initial parameter seeding is developed and tested. Methods: Different fitting algorithms that use variations and combinations of Simplex-optimization, Genetic Algorithm and Particle Swarm are tested against simulated data with brief events removed as in real resolution limited data. Results: A two-step fitting algorithm that uses Particle Swarm optimization to find initial parameters and then a modified Simplex approach to fine-adjust the initial parameters successfully find the correct rates used for data simulation. Conclusions: SCAIM (Single Channel Analysis in MATLAB) facilitate the deduction of kinetic schemes underlying single-channel data.