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Model of the hyperpolarization-activated current Ih and its regulation by calciumWith Agnessa Babloyantz (University of Brussels, Belgium), we introduced a biophysical model of the hyperpolarization-activated current Ih to account for the unusual kinetic features of this current [1]. This model allowed us to account for several features of the oscillatory behavior of thalamocortical neurons. The model included a dual gating process of the channel, with a fast and a slow gate. This combination of fast and slow gates allowed the model to reproduce the unusual features of Ih in voltage-clamp experiments [1].In a subsequent study with Terrence Sejnowski (Salk Institute, USA), we introduced a regulation of Ih by intracellular calcium [2], inspired from results in cardiac electrophysiology. The model consisted of a selective binding of calcium ions to the open state of the Ih channel, leading to prolongation of its opening time, and a shift of its steady-state activation characteristics in the presence of calcium [2]. Coupled with the T-type calcium current, this model of Ih allowed us to reproduce a variety of oscillatory states in thalamic neurons, such as waxing-and-waning oscillations [2]. A more elaborate model was introduced later [3], based on the indirect regulation of Ih channels by calcium, through a second messenger (for example cAMP). This model reproduced realistically the oscillatory behavior of thalamic neurons and networks [3]. A similar model also reproduced a form of persistent activity activated by hyperpolarization (HAGPA) [4] (see Section 2.3). Alain Destexhe |