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Paper Information

Journal:   JOURNAL OF MEDICINAL PLANTS   March 2004 , Volume 3 , Number 9; Page(s) 55 To 68.
 
Paper: 

INHIBITION OF SUSTAINED REPETITIVE FIRING (SRF) IN CULTRES HIPPOCAMPAL NEURONS BY AN AQUEONS FRACTION ISOLATED FROM DELPHINIUM DENUDATUM WALL.EX HOOK.F & THOMS

 
 
Author(s):  HAIDARY R.*, SHAHEEN F., SOMBATI S., LORENZO RJD
 
* Endocrinology and Metabolism Research Center, Dr.Shariati Hospital
 
Abstract: 
In this report we investigated the effects of the aqueous fraction (AF) isolated from Delphinium denudatum on Sustained Repetitive Firing (SRF) in cultured neonatal rat hippocampal pyramidal neurons. Blockade of SRF is one of the basic mechanisms of antiepileptic drugs (AED) at the cellular level. The effects of aqueous fraction (0.2-0.6 mg/ml) were compared with the prototype antiepileptic drugs (AED) at the cellular level. The effects of aqueous fraction (0.2-0.6 mg/mg) were compared with the prototype antiepileptic drug, phenytion (PHT). Using the whole cell current-clamp technique, Sustained repetitive Firing was elicited in neurons by a depolarizing pulse of 500 ms duration, 0.3 Hz and 0.1-0.6 nA current strength. Similar to phenytion, aqueous fraction reduced the number of action potentials (AP) per pulse in a concentration-dependent manner until no action potentials were elicited for the remainder of the pulse. There was a corresponding use-dependent reduction in amplitude and V__max (velocity of upstroke) of action potentials. The V__max and amplitude of the first action potential was not affected by phenytion, while aqueous fraction exhibited concentration-dependent reduction. At 0.6 mg/ml aqueous fraction reduced V_max to 58-63% and amplitude to 16-20% of the control values. The blockade of Sustained Repetitive Firing by aqueous fraction was reversed with hyperpolarization of membrane potential (-65 to -76 mV) while depolarization of membrane potential (-53mV to -48mV) potentiated the block. The results suggest that aqueous fraction blocks Sustained Repetitive Firing in hippocampal neurons in a use-dependent and voltage-dependent manner similar to phenytion. However, unlike phenytion, which interacts preferably with the inactive stateof the Na^+channel, the compounds present in aqueous fraction apparently also interact with the resting state of the Na^+ channels as suggested by dose-dependent reduction of V__max and amplitude of first AP .We conclude that aqueous fraction contains potent anticonvulsant compounds.
 
Keyword(s): DELPHINIUM DENUDATUM, ANTICONVULSANT ACTIVITY, HIPPOCAMPUS, SUSTAINED REPETITVE FIFRING, EPILEPSY
 
References: 
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