A dynamic clamp protocol to artificially modify cell capacitance

Abstract

Dynamics of excitable cells and networks depend on the membrane time constant, set by membrane resistance and capacitance. Whereas pharmacological and genetic manipulations of ionic conductances of excitable membranes are routine in electrophysiology, experimental control over capacitance remains a challenge. Here, we present capacitance clamp, an approach that allows electrophysiologists to mimic a modified capacitance in biological neurons via an unconventional application of the dynamic clamp technique. We first demonstrate the feasibility to quantitatively modulate capacitance in a mathematical neuron model and then confirm the functionality of capacitance clamp in in vitro experiments in granule cells of rodent dentate gyrus with up to threefold virtual capacitance changes. Clamping of capacitance thus constitutes a novel technique to probe and decipher mechanisms of neuronal signaling in ways that were so far inaccessible to experimental electrophysiology.

In Situ Synthesis and Assembly of Functional Materials and Devices in Living Systems

“…80 Dynamic clamp results have indeed validated that decreasing the capacitance can increase the neuron sensitivity and vice versa. 81 By interfacing neuron membranes with electroactive materials and genetically targeting their assembly, we can precisely control membrane capacitance, similar to the control achieved in chemogenetics or optogenetics.…”

Effects of nonlinear membrane capacitance in the Hodgkin-Huxley model of action potential on the spike train patterns of a single neuron

“…On the other hand, there is evidence in favor of capacitance depending nonlinearly on the membrane potential difference [7][8][9][10][11][12][13]. A recent study presented the Cap-Clamp techniques to clamp the dynamic capacitance [14] in in vitro experiments, motivated by the successful dynamic clamp method of Robinson (1994) and Sharp et al (1993) [15,16]. In this new technique the capacitance is varied dynamically albeit virtually, thereby enabling a simulation study of subtle electrical traits of a physical neuron [14].…”

“…A recent study presented the Cap-Clamp techniques to clamp the dynamic capacitance [14] in in vitro experiments, motivated by the successful dynamic clamp method of Robinson (1994) and Sharp et al (1993) [15,16]. In this new technique the capacitance is varied dynamically albeit virtually, thereby enabling a simulation study of subtle electrical traits of a physical neuron [14]. The nonlinear capacitance for solvent-free uncharged bilayer membrane can be estimated from the Atomistic Molecular Dynamics Simulations of Zwitterionic Lipid Bilayers [17].…”