ID 385 - Temperature dependent changes in HCN channel current (Ih) in human motor axons of different threshold. Implications for generation of febrile seizures

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• 作者：C.E.G. Moore^a ; ^b ; H.J. Cockerill^a ; ^c ; O. Marmoy^a ; ^c
• 刊名：Clinical Neurophysiology
• 出版年：2016
• 出版时间：March 2016
• 年：2016
• 卷：127
• 期：3
• 页码：e58
• 全文大小：36 K

文摘

Mechanisms underlying seizure initiation are complex. Hyperthermia increases pyramidal cell activity and mutations in the hyperpolarisation-activated-cyclic-nucleotide-modulated-channels-(HCN) in patients with febrile seizures show temperature dependent changes in channel kinetics. Changes of axonal excitability in response to hyperthermia was studied in vivo, in human.

Methods

Axonal excitability of high (40%) and low (10–20%) threshold motor axons was assessed before and after warming (6 °C). Temperature was maintained using a waterbath and measured using a thermistor placed near the stimulating cathode.

Results

Seven female subjects were studied with ethics committee approval. At 40% tracking, axonal excitability showed reduced superexcitability, faster accommodation to depolarization and reduced accommodation to hyperpolarisation (Howells et al., 2013). Low threshold fibers showed the same changes with the marked exception of the response to hyperpolarisation which was significantly increased (p < 0.02).

Conclusions

The effect of hyperthermia on inward rectification to hyperpolarisation (HCN channel function) is increased in low threshold fibers and decreased in higher threshold fibers. Higher HCN function (I_h current) increases resting membrane potential in low threshold fibers.

Key message

This temperature related increase in Ih may contribute to initiation of seizures. Modulation of HCN channels may be a novel target for drug development in epilepsy.