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Specific contributionof human T‐typecalcium channelisotypes (α1G, α1Hand α1I) to neuronalexcitability Jean CheminArnaud MonteilEdward Perez‐Reyes2002 год

Specific contribution of human T‐type calcium channel isotypes (α1G, α1H and α1I) to neuronal excitability
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Аннотация: In several types of neurons, firing is an intrinsic property produced by specific classes of ion channels. Low‐voltage‐activated T‐type calcium channels (T‐channels), which activate with small membrane depolarizations, can generate burst firing and pacemaker activity. Here we have investigated the specific contribution to neuronal excitability of cloned human T‐channel subunits. Using HEK‐293 cells transiently transfected with the human α 1G (Ca V 3.1), α 1H (Ca V 3.2) and α 1I (Ca V 3.3) subunits, we describe significant differences among these isotypes in their biophysical properties, which are highlighted in action potential clamp studies. Firing activities occurring in cerebellar Purkinje neurons and in thalamocortical relay neurons used as voltage clamp waveforms revealed that α 1G channels and, to a lesser extent, α 1H channels produced large and transient currents, while currents related to α 1I channels exhibited facilitation and produced a sustained calcium entry associated with the depolarizing after‐potential interval. Using simulations of reticular and relay thalamic neuron activities, we show that α 1I currents contributed to sustained electrical activities, while α 1G and α 1H currents generated short burst firing. Modelling experiments with the NEURON model further revealed that the α 1G channel and α 1I channel parameters best accounted for T‐channel activities described in thalamocortical relay neurons and in reticular neurons, respectively. Altogether, the data provide evidence for a role of α 1I channel in pacemaker activity and further demonstrate that each T‐channel pore‐forming subunit displays specific gating properties that account for its unique contribution to neuronal firing.
Год издания: 2002
Авторы: Jean Chemin, Arnaud Monteil, Edward Perez‐Reyes, Emmanuel Bourinet, Joël Nargeot, Philippe Lory
Издательство: Wiley
Источник: The Journal of Physiology
Ключевые слова: Ion channel regulation and function, Neuroscience and Neuropharmacology Research, Cardiac electrophysiology and arrhythmias
Другие ссылки: The Journal of Physiology (HTML)
PubMed Central (HTML)
PubMed (HTML)