Interconversion kinetics of ion channels

The generation and propagation of action potentials is mediated by voltage-gated cation channels that confer electrical conductivity to the membrane of excitable cells. In neurons for example, sodium channels modulate the membrane potential in response to electrical stimuli, which makes them important targets for toxins and therapeutic drugs. While the general behavior of isolated channels is reasonably well understood, their collective response in vivo is not. Indeed, a network of neurons is characterized by irregular action potential firing patterns that do not result from the integration of known intra- and inter-neuron signals.

We aim to build a dynamical picture of voltage-gated ion channels from atomistic simulations and reconcile local activity (action potential and postsynaptic excitation) to macroscopic current measurements in neuronal systems.

Single channel and macroscopic current measurements reveal intrinsic (neuron dependent) and extrinsic (network dependent) noise in membrane conductance. This means that channels let ions through the membrane with varying efficiency, which causes delays in synaptic transmission and affects the overall timing of action potentials within a network.

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We develop methods to provide a dynamical picture of functional sodium channels. The goal is to derive a macroscopic model of neuronal activity that is directly linked to the ab initio transition paths for interconversion between the open, closed, and inactive sodium channel states and a mesoscopic description of signal transmission across synapses. 

Kinetic model of the eukaryotic voltage-dependent sodium channels in neurons. 

Atomistic model of the ion channel where the membrane potential is modeled by an electric field.

In addition to its fundamental importance, a true multiscale model of neuron network will pave the way toward a unified theory of brain activity that can help identify and resolve known disorders in neuroscience and medicine.