MUSCARINIC RECEPTOR ACTIVATION INDUCES A PROLONGED POSTSTIMULUS AFTERDEPOLARIZATION WITH A CONDUCTANCE DECREASE IN GUINEA-PIG OLFACTORY CORTEX NEURONS INVITRO

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-mu-M), a slowly-decaying afterdepolarization (sADP) accompanied by sustained repetitive firing was induced following a long depolarizing stimulus. The corresponding slow inward current (I(ADP)) revealed under voltage clamp behaved like a K+-mediated tail current, but was associated with a decreased membrane conductance. I(ADP) was insensitive to tetrodotoxin (TTX), Ba2+, Cs+, or 4-aminopyridine (4-AP), but was blocked by 500-mu-M TEA or TBA (tetrabutylammonium). The OXO-M response and I(ADP) were also reduced by Cd2+ or Ca2+-free solution, suggesting a dependence on Ca2+-entry. We propose that OXO-M induces a novel outward K+ current that can be slowly de-activated by Ca2+-entry during a depolarizing stimulus. Summation of I(ADP) tail currents could contribute to the sustained muscarinic excitation of mammalian cortical neurones.