Lidocaine Blocks the Hyperpolarization-activated Mixed Cation Current, I h, in Rat Thalamocortical Neurons
Bibliographic record
Abstract
BACKGROUND: The mechanisms that underlie the supraspinal central nervous system effects of systemic lidocaine are poorly understood and not solely explained by Na(+) channel blockade. Among other potential targets is the hyperpolarization-activated cation current, I(h), which is blocked by lidocaine in peripheral neurons. I(h) is highly expressed in the thalamus, a brain area previously implicated in lidocaine's systemic effects. The authors tested the hypothesis that lidocaine blocks I(h) in rat thalamocortical neurons. METHODS: The authors conducted whole cell voltage- and current-clamp recordings in ventrobasal thalamocortical neurons in rat brain slices in vitro. Drugs were bath-applied. Data were analyzed with Student t tests and ANOVA as appropriate; α = 0.05. RESULTS: Lidocaine voltage-independently blocked I(h), with high efficacy and a half-maximal inhibitory concentration (IC(50)) of 72 μM. Lidocaine did not affect I(h) activation kinetics but delayed deactivation. The I(h) inhibition was accompanied by an increase in input resistance and membrane hyperpolarization (maximum, 8 mV). Lidocaine increased the latency of rebound low-threshold Ca(2+) spike bursts and reduced the number of action potentials in bursts. At depolarized potentials associated with the relay firing mode (>-60 mV), lidocaine at 600 μM concurrently inhibited a K(+) conductance, resulting in depolarization (7-10 mV) and an increase in excitability mediated by Na(+)-independent, high-threshold spikes. CONCLUSIONS: Lidocaine concentration-dependently inhibited I(h) in thalamocortical neurons in vitro, with high efficacy and a potency similar to Na(+) channel blockade. This effect would reduce the neurons' ability to produce intrinsic burst firing and δ rhythms and thereby contribute to the alterations in oscillatory cerebral activity produced by systemic lidocaine in vivo.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".