Anticonvulsant effect of dipropofol by enhancing native GABA currents in cortical neurons in mice.
Jingliang ZhangXiaoling ChenMatti KårbøYi ZhaoLong AnRutao WangKeWei WangZhuo HuangPublished in: Journal of neurophysiology (2018)
Temporal lobe epilepsy (TLE), the most common pharmacoresistant focal epilepsy disorder, remains a major unmet medical need. Propofol is used as a short-acting medication for general anesthesia and refractory status epilepticus with issues of decreased consciousness and memory loss. Dipropofol, a derivative of propofol, has been reported to exert antioxidative and antibacterial activities. Here we report that dipropofol exerted anticonvulsant activity in a mouse model of kainic acid-induced seizures. Whole cell patch-clamp recordings of brain slices from the medial entorhinal cortex (mEC) revealed that dipropofol hyperpolarized the resting membrane potential and reduced the number of action potential firings, resulting in suppression of cortical neuronal excitability. Furthermore, dipropofol activated native tonic GABAA currents of mEC layer II stellate neurons in a dose-dependent manner with an EC50 value of 9.3 ± 1.6 μM (mean ± SE). Taken together, our findings show that dipropofol activated GABAA currents and exerted anticonvulsant activities in mice, thus possessing developmental potential for new anticonvulsant therapy. NEW & NOTEWORTHY The anticonvulsant effect of dipropofol was shown in a mouse model of kainic acid-induced seizures. Whole cell patch-clamp recordings of brain slices showed suppression of cortical neuronal excitability by dipropofol. Dipropofol activated the native tonic GABAA currents in a dose-dependent manner.
Keyphrases
- temporal lobe epilepsy
- mouse model
- single cell
- cerebral ischemia
- healthcare
- resting state
- cell therapy
- white matter
- functional connectivity
- high fat diet induced
- transcranial direct current stimulation
- heart rate
- human health
- type diabetes
- working memory
- heart rate variability
- multiple sclerosis
- emergency department
- blood pressure
- blood brain barrier
- adverse drug
- silver nanoparticles
- climate change
- brain injury
- bone marrow
- skeletal muscle
- wild type
- water soluble