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Quantifying activation delay and the Cole-More shift via current derivatives.

Bernardo I Pinto-Anwandter¹, Francisco Bezanilla²

¹Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois.

Biophysical Journal

|December 8, 2025

Summary

This summary is machine-generated.

Analyzing ion channel kinetics is simplified by measuring the current derivative (dI/dt). This method accurately quantifies activation delay and the Cole-Moore shift in voltage-gated potassium channels.

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Area of Science:

Biophysics
Computational Neuroscience
Ion Channel Physiology

Background:

Ion channel kinetics involve transitions between closed and open states, often showing sigmoidal activation.
The Cole-Moore shift describes the delay in activation kinetics influenced by prior hyperpolarization.
Current methods for measuring activation delay and Cole-Moore shift are complex and lack closed-form expressions.

Purpose of the Study:

To introduce a straightforward method for quantifying ion channel activation delay and the Cole-Moore shift.
To utilize the time derivative of the current (dI/dt) as a novel descriptor for these kinetic parameters.
To demonstrate the applicability of this method across various voltage-gated channel systems.

Main Methods:

Calculating the time derivative of ionic current (dI/dt) during channel activation.
Identifying the maximum of the dI/dt trace as a measure of activation delay.
Applying the method to experimental data from Shaker voltage-gated potassium channels.

Main Results:

The maximum of the current derivative (dI/dt) directly corresponds to the inflection point of the activation curve.
This method provides a simple, quantitative, and generalizable descriptor for activation delay.
The approach remains effective even in the presence of channel inactivation or multicomponent kinetics.

Conclusions:

Measuring the maximum of the current derivative offers a robust and broadly applicable tool for analyzing ion channel activation delay and the Cole-Moore shift.
This technique simplifies kinetic analysis and facilitates integration into computational models.
The proposed method enhances the understanding of voltage-gated channel behavior.