Enhancement of cyclic AMP-dependent sodium current by the convulsant drug pentylenetetrazol.
The convulsant drug pentylenetetrazol (PTZ) causes paroxysmal depolarizing shifts (PDS) and bursting in molluscan neurons. PDS has been found to be accompanied by increased levels of cyclic AMP (cAMP) and supported by persistent Na+ current. In neurons of the snail Lymnaea stagnalis the blocker of cAMP degradation isobutylmethylxanthine (IBMX) mimicks PTZ action. Na+ dependence of PTZ-induced inward shift in holding current in voltage-clamped cells supports the potential Na+ current origin of PDS. Intracellular cAMP injection elicits a transient Na+ current whose amplitude and duration are enhanced by both PTZ and IBMX. PTZ may cause PDS partly through slowing cAMP degradation, thus enhancing the cAMP-dependent Na+ current. PDS-generated bursts cause partial inactivation of the Na+ current, which may contribute towards burst termination.
McCrohan
C R
CR
Department of Physiological Sciences, University of Manchester, U.K.
Gillette
R
R
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002413:Cations, Divalent / Q000494:pharmacology; D003292:Convulsants / Q000494:pharmacology*; D000242:Cyclic AMP / Q000494:pharmacology / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D010433:Pentylenetetrazole / Q000494:pharmacology*; D012908:Snails / Q000187:drug effects / Q000502:physiology*; D012964:Sodium / Q000502:physiology*
D002413:Cations, Divalent; D003292:Convulsants; D012964:Sodium; D000242:Cyclic AMP; D015056:1-Methyl-3-isobutylxanthine; D010433:Pentylenetetrazole