4.6 Article

Different kinetic properties of two T-type Ca2+ currents of rat reticular thalamic neurones and their modulation by enflurane

Journal

JOURNAL OF PHYSIOLOGY-LONDON
Volume 566, Issue 1, Pages 125-142

Publisher

WILEY
DOI: 10.1113/jphysiol.2005.086579

Keywords

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Funding

  1. NIDA NIH HHS [K08 DA000428, K08-DA00428] Funding Source: Medline
  2. NIGMS NIH HHS [R01 GM066181, R01 GM070726, R01GM070726] Funding Source: Medline

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Currents arising from T-type Ca2+ channels in nucleus reticularis thalami (nRT) play a critical role in generation of low-amplitude oscillatory bursting involving mutually interconnected cortical and thalamic neurones, and are implicated in the state of arousal and sleep, as well as seizures. Here we show in brain slices from young rats that two kinetically different T-type Ca2+ currents exist in nRT neurones, with a slowly inactivating current expressed only on proximal dendrites, and fast inactivating current predominantly expressed on soma. Nickel was about twofold more potent in blocking fast (IC50 64 mu m) than slow current (IC50 107 mu m). The halogenated volatile anaesthetic enflurane blocked both currents, but only the slowly inactivating current was affected in voltage-dependent fashion. Slow dendritic current was essential for generation of low-threshold Ca2+ spikes (ITS), and both enflurane and nickel also suppressed LTS and neuronal burst firing at concentrations that blocked isolated T currents. Differential kinetic properties of T currents expressed in cell soma and proximal dendrites of nRT neurones indicate that various subcellular compartments may exhibit different membrane properties in response to small membrane depolarizations. Furthermore, since blockade of two different T currents in nRT neurones by enflurane and other volatile anaesthetics occurs within concentrations that are relevant during clinical anaesthesia, our findings suggest that these actions could contribute to some important clinical effects of anaesthetics.

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