ArticleNeuropharmacology2012
Inhibition of T-type calcium current in rat thalamocortical neurons by isoflurane.
Article in Neuropharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- Article
- Controversies in anesthesia-induced developmental neurotoxicity.Best practice & research. Clinical anaesthesiology · 2023Review
- Sex-specific hypnotic effects of the neuroactive steroid (3β,5β,17β)-3-hydroxyandrostane-17-carbonitrile are mediated by peripheral metabolism into an active hypnotic steroid.British journal of anaesthesia · 2023Article
- Thalamic T-Type Calcium Channels as Targets for Hypnotics and General Anesthetics.International journal of molecular sciences · 2022Review
- General Anesthesia and the Young Brain: The Importance of Novel Strategies with Alternate Mechanisms of Action.International journal of molecular sciences · 2022Review
- Synthetic neuroactive steroids as new sedatives and anaesthetics: Back to the future.Journal of neuroendocrinology · 2022Review
- The Effects of General Anesthetics on Synaptic Transmission.Current neuropharmacology · 2020Review
- Alterations in Oscillatory Behavior of Central Medial Thalamic Neurons Demonstrate a Key Role of CaV3.1 Isoform of T-Channels During Isoflurane-Induced Anesthesia.Cerebral cortex (New York, N.Y. : 1991) · 2019Article
- The Biology of General Anesthesia from Paramecium to Primate.Current biology : CB · 2019Review
- Novel neurosteroid hypnotic blocks T-type calcium channel-dependent rebound burst firing and suppresses long-term potentiation in the rat subiculum.British journal of anaesthesia · 2019Article
- CaNeuropharmacology · 2018Article
- A neurosteroid analogue with T-type calcium channel blocking properties is an effective hypnotic, but is not harmful to neonatal rat brain.British journal of anaesthesia · 2018Article
- Layer- and subregion-specific differences in the neurophysiological properties of rat medial prefrontal cortex pyramidal neurons.Journal of neurophysiology · 2018Article
- Heantos-4, a natural plant extract used in the treatment of drug addiction, modulates T-type calcium channels and thalamocortical burst-firing.Molecular brain · 2016Article
- Dynamic Analysis of the Conditional Oscillator Underlying Slow Waves in Thalamocortical Neurons.Frontiers in neural circuits · 2016Article
- Awake vs. anesthetized: layer-specific sensory processing in visual cortex and functional connectivity between cortical areas.Journal of neurophysiology · 2015Article
- Hyperexcitability of rat thalamocortical networks after exposure to general anesthesia during brain development.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Essential thalamic contribution to slow waves of natural sleep.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013Article
- Mapacalcine protects mouse neurons against hypoxia by blocking cell calcium overload.PloS one · 2013Article
- Article
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Thalamocortical (TC) neurons provide the major sensory input to the mammalian somatosensory cortex. Decreased activity of these cells may be pivotal in the ability of general anesthetics to induce loss of consciousness and promote sleep (hypnosis). T-type voltage-gated calcium currents (T-currents) have a key function regulating the cellular excitability of TC neurons and previous studies have indicated that volatile general anesthetics may alter the excitability of these neurons. Using a patch-clamp technique, we investigated the mechanisms whereby isoflurane, a common volatile anesthetic, modulates isolated T-currents and T-current-dependent excitability of native TC neurons in acute brain slices of the rat. In voltage-clamp experiments, we found that isoflurane strongly inhibited peak amplitude of T-current, yielding an IC(50) of 1.1 vol-% at physiological membrane potentials. Ensuing biophysical studies demonstrated that inhibition was more prominent at depolarized membrane potentials as evidenced by hyperpolarizing shifts in channel availability curves. In current-clamp experiments we found that isoflurane decreased the rate of depolarization of low-threshold-calcium spikes (LTCSs) and consequently increased the latency of rebound spike firing at the same concentrations that inhibited isolated T-currents. This effect was mimicked by a novel selective T-channel blocker 3,5-dichloro-N-[1-(2,2-dimethyl-tetrahydro-pyran-4-ylmethyl)-4-fluoro-piperidin-4-ylmethyl]-benzamide (TTA-P2). In contrast, isoflurane and TTA-P2 had minimal effect on resting membrane potential and cell input resistance. We propose that the clinical properties of isoflurane may at least partly be provided by depression of thalamic T-currents.
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Registered trials
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