Five ADNFLE mutations reduce the Ca2+ dependence of the mammalian alpha4beta2 acetylcholine response.

Five nicotinic acetylcholine receptor (nAChR) mutations are currently linked to autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). The similarity of their clinical symptoms suggests that a common functional anomaly of the mutations underlies ADNFLE seizures. To identify this anomaly, we constructed rat orthologues (S252F, +L264, S256L, V262L, V262M) of the human ADNFLE mutations, expressed them in Xenopus oocytes with the appropriate wild-type (WT) subunit (alpha4 or beta2), and studied the Ca2+ dependence of their ACh responses.

Nicotine trapping causes the persistent desensitization of alpha4beta2 nicotinic receptors expressed in oocytes.

To determine whether prolonged nicotine exposure persistently inactivates rat alpha4beta2 nicotinic receptors expressed in Xenopus oocytes, we measured the voltage-clamped alpha4beta2 response to acetylcholine (ACh) before and 24 h after, 1-h or 12-h incubations in 10 microm nicotine. A 12-h incubation in 10 microm nicotine depressed the alpha4beta2 ACh response for 24 h without affecting total or surface alpha4beta2 expression. To determine whether oocyte-mediated nicotine release caused this depression, we co-incubated an alpha4beta2-expressing oocyte with an un-injected one (pre-incubated in 10 microm nicotine for 12 h) for 24 h and measured the change in the alpha4beta2 ACh response.

Quality of life in psychogenic nonepileptic seizures.

Purpose: Psychogenic nonepileptic seizures (PNESs) are events that alter or seem to alter the neurologic function and, in their appearance, resemble epileptic seizures (ESs). In patients with ESs the psychological and medical aspects of epilepsy greatly influence the health-related quality of life (HRQOL). The relation between these factors and PNESs is not well established.