Muscarinic receptor activation induces a prolonged post-stimulus afterdepolarization with a conductance decrease in guinea-pig olfactory cortex neurones in vitro.
The persistent excitation of guinea-pig olfactory cortical neurones in vitro by the muscarinic agonist oxotremorine-M (OXO-M) was investigated. In OXO-M (10-20 microM), a slowly-decaying afterdepolarization (sADP) accompanied by sustained repetitive firing was induced following a long depolarizing stimulus. The corresponding slow inward current (IADP) revealed under voltage clamp behaved like a K(+)-mediated tail current, but was associated with a decreased membrane conductance. IADP was insensitive to tetrodotoxin (TTX), Ba2+, Cs+, or 4-aminopyridine (4-AP), but was blocked by 500 microM TEA or TBA (tetrabutylammonium). The OXO-M response and IADP were also reduced by Cd2+ or Ca(2+)-free solution, suggesting a dependence on Ca(2+)-entry. We propose that OXO-M induces a novel outward K+ current that can be slowly de-activated by Ca(2+)-entry during a depolarizing stimulus. Summation of IADP tail currents could contribute to the sustained muscarinic excitation of mammalian cortical neurones.
Constanti
A
A
Department of Pharmacology, School of Pharmacy, London, U.K.
Bagetta
G
G
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology*; D002586:Cesium / Q000494:pharmacology; D004553:Electric Conductivity / Q000187:drug effects; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010095:Oxotremorine / Q000494:pharmacology*; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*; D012903:Smell; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
D000644:Quaternary Ammonium Compounds; D011976:Receptors, Muscarinic; D013757:Tetraethylammonium Compounds; D002586:Cesium; D001464:Barium; D013779:Tetrodotoxin; D010095:Oxotremorine; D019789:Tetraethylammonium; D015761:4-Aminopyridine; C009405:tetrabutylammonium