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| The standard method for characterising ion channels in neurons is voltage clamp in patch clamp recordings [1]. However, in the classical procedure measurements are performed with constant voltage steps and chemical channel blockers are used to isolate individual ion channel types. Because chemical blockers can be irreversible, different ion channels of the same neuron type have to be measured in different individual cells, potentially even in separate preparations from different individual animals. This can be highly problematic and it has been observed that so combining measurements from many different cells does not allow to build accurate whole cell models [2]. Here we introduce a proposal to go beyond the classical constant steps and try to design optimised stimulation patterns to isolate the effect of different ion channels without blockers. Furthermore, we propose to use closed-loop online parameter estimation methods with simulated ``dynamic clamp'' coupling to then build a model of all ionic currents in an individual neuron simultaneously. If successful this new closed-loop experimentation technology could have deep impacts on our understanding of how individual neurons vary in their ion channel content.
[1] Dunlop J, Bowlby M, Peri R, Vasilyev D, Arias R. (2008) Nature Reviews Drug Discovery 7:358-368.
[2] Golowasch J, Goldman MS, Abbott LF, Marder E. (2002) J Neurophysiol. 87(2):1129-1131. |
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