Block of spontaneous termination of paroxysmal depolarizations by forskolin (buccal ganglia, Helix pomatia).
Effects of cAMP-activated protein kinases (PKA) on epileptic activity are at present studied in a model nervous system. Identified neurons in the buccal ganglia of the snail Helix pomatia were recorded with intracellular microelectrodes in a continuously perfused experimental chamber. Epileptiform activity appeared regularly in neuron B3 when the saline contained pentylenetetrazol (20-40 mM). Epileptiform activity consisted of a series of paroxysmal depolarization shifts (PDS). Epileptiform activity was quantified by calculating the percentage of PDS-duration of PDS-periods. High percentage of PDS-duration was regularly found 15-30 min after the start of treatment with pentylenetetrazol. Subsequently, percentage of PDS decreased spontaneously. Adding forskolin (50 microM) to the pentylenetetrazol-containing solution increased percentage of PDS-duration. The increase during forskolin corresponded to the amount of decrease which had taken place spontaneously before. During application of forskolin for up to 4 h, spontaneous PDS decrease was absent, i.e., epileptiform activity corresponded to status epilepticus. Forskolin was not able to induce epileptiform activity when applied without pentylenetetrazol. 1,6-Dideoxy-forskolin (50 microM) did not accelerate epileptiform activity. When pentylenetetrazol was applied twice (1 h each) separated by 2.5 h of control conditions, PDS decrease obtained during the first application was found to be largely preserved during control conditions. When forskolin was applied for 30 min in between both applications of pentylenetetrazol, the second response to pentylenetetrazol did not show a preserved PDS decrease. Results suggest that forskolin blocks an endogenous antiepileptic process and that activation of PKA can maintain epileptic activity and induce status epilepticus.
Ure
Atik
A
Institute of Experimental Epilepsy Research, University of Münster, Hüfferstrabe 68, Germany.
Altrup
Ulrich
U
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D005576:Colforsin / Q000031:analogs & derivatives / Q000494:pharmacology*; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D004827:Epilepsy / Q000139:chemically induced / Q000473:pathology; D017952:Ganglia, Invertebrate / Q000166:cytology*; D006372:Helix, Snails; D008959:Models, Neurological; D009474:Neurons / Q000187:drug effects*; D010433:Pentylenetetrazole / Q000494:pharmacology; D013997:Time Factors
D005576:Colforsin; C047983:1,9-dideoxyforskolin; D010433:Pentylenetetrazole