Anticonvulsant actions of gap junctional blockers in an in vitro seizure model.
Gap junctions (gjs) are increasingly recognized as playing a significant role in seizures. We demonstrate that different types of gap junctional blocking agents reduce the duration of evoked seizure-like primary afterdischarges (PADs) in the rat in vitro CA1 hippocampal pyramidal region, following repetitive tetanization of the Schaffer collaterals. Intracellular acidosis, which is known to block gap junctional communication, decreased the PADs, whereas alkalinization increased the PADs. Cellular excitability was not significantly depressed as determined by input/output relations recorded before and during perfusion of the gj blockers blockers carbenoxolone and sodium propionate. There was a small decrease following 1-octanol perfusion and a large decrease following NH(4)Cl application. Carbenoxolone diminished PAD duration, but increased neuronal excitability in whole-cell recordings. After robust PADs were established, the expression of several gj proteins including connexins (Cxs) 26, 32, 36, and 43, as measured by Western blotting, was unchanged, although the level of nonphosphorylated Cx43 was decreased. Our data support the concept that blocking gap junctional communication is an anticonvulsant mechanism.
D020003:1-Octanol / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002229:Carbenoxolone / Q000494:pharmacology*; D017630:Connexins / Q000032:analysis; D004558:Electric Stimulation; D004827:Epilepsy / Q000188:drug therapy*; D017629:Gap Junctions / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D006624:Hippocampus / Q000503:physiopathology; D066298:In Vitro Techniques; D018408:Patch-Clamp Techniques; D011422:Propionates / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014635:Valproic Acid / Q000494:pharmacology
D000927:Anticonvulsants; D017630:Connexins; D011422:Propionates; D000643:Ammonium Chloride; D014635:Valproic Acid; C514135:sodium propionate; C029658:propionic acid; D002229:Carbenoxolone; D020003:1-Octanol