[Regulation of the activity of monoaminergic neurons by ion channels: an opportunity for new therapeutic approaches?].
Small-conductance ca2+ -activated potassium (SK) channels underlie one component of the afterhyperpolarization which follows one or several action potentials in neurons. Their blockade enhances neuronal excitability and, in some cases, produces a significant depolarization within dendrites. Three subtypes of SK subunits exist and are differentially expressed in the brain. We have developed SK channel blockers, we have characterized their potency and have used some of them as pharmacological tools. Moreover, we have shown that SK channel blockade increases dopaminergic and serotonergic, but not noradrenergic transmission. We believe that this is an original way of modulating brain function. Our next goal is to find subtype-selective blockers, using a variety of approaches, including molecular modelling.
Seutin
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Laboratorie de Pharmacologie, Centre de Recherches en Neurobiologie Cellulaire et Moléculaire.
D000200:Action Potentials / Q000502:physiology; D015306:Biogenic Monoamines / Q000502:physiology*; D006801:Humans; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D001523:Mental Disorders / Q000188:drug therapy / Q000503:physiopathology; D009422:Nervous System Diseases / Q000188:drug therapy / Q000503:physiopathology*; D009474:Neurons / Q000502:physiology*; D010300:Parkinson Disease / Q000188:drug therapy / Q000503:physiopathology; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000502:physiology
D015306:Biogenic Monoamines; D007473:Ion Channels; D051640:Small-Conductance Calcium-Activated Potassium Channels