Calcium-activated potassium conductance. An alternative to the dopamine hypothesis of neuroleptic action?
Neuroleptics are structurally a heterogenous group of compounds which possess antipsychotic activity. They increase dopamine metabolites by blocking dopamine receptors and enhancing presynaptic turnover. This forms the cornerstone of the dopamine hypothesis of neuroleptic action, which is supported by wide-ranging behavioural, physiological and biochemical studies. It is, however, clear that neuroleptics are far less specific for the dopamine receptor than was previously considered. They influence a range of neuronal activities, including calcium-activated potassium conductance, which governs the rate of action potential generation by many neurones. Recent physiological studies indicate that all commonly used neuroleptics alter calcium-activated potassium conductance in central neurones, in concentrations similar to those achieved clinically. An adaptive increase in calcium-activated potassium conductance mechanisms in key sensory processing neurones would render the psychotic patient less susceptible to bombardment by environmental stimuli. This action may explain in part the therapeutic effect of neuroleptics.
D000200:Action Potentials; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D002118:Calcium / Q000378:metabolism*; D006801:Humans; D007473:Ion Channels / Q000187:drug effects; D009474:Neurons / Q000502:physiology; D011188:Potassium / Q000378:metabolism*; D011954:Receptors, Dopamine / Q000187:drug effects; D012559:Schizophrenia / Q000188:drug therapy / Q000503:physiopathology
D014150:Antipsychotic Agents; D007473:Ion Channels; D011954:Receptors, Dopamine; D011188:Potassium; D002118:Calcium