Relationship between large conductance calcium-activated potassium channel and bursting activity

To elucidate the role of the large conductance calcium-activated potassium channel (BKCa channel) in the production of bursting activity, which is characteristic of convulsions, effects of iberiotoxin (IbTX), a selective blocker of the BKCa channel, on bursting activity, induced by various procedures were examined using primary cultured neurons from the cerebral cortex of mice. IbTX completely inhibited bursting activity induced by pentylenetetrazol (PTZ), caffeine, 1,4,5-triphosphate (IP3) and direct forced increase of intracellular calcium. Inherent spontaneous bursting activity in the cerebral cortical neurons of the E1 mouse, which shows a high susceptibility to convulsions was also completely inhibited by IbTX. Apamin, a specific blocker of the small conductance calcium-activated potassium channel (SKCa channel) showed no inhibition of bursting activity. These findings suggest that the BKCa channel is essential for the production of bursting activity, and also suggest the possibility of clinical use of blocking agents of the BKCa channel against intractable epilepsy. (C) 2000 Elsevier Science B.V. All rights reserved.