Modulation of muscarinic facilitation of epileptiform discharges in immature rat neocortex

摘要: Abstract We examined the cholinergic effects on epileptiform discharge generation in immature (postnatal days 10–20) rat neocortex. Evoked and spontaneous field potentials were recorded from deep layers of neocortical slices during GABA A receptor blockade by bicuculline methiodide (BMI, 50 μM). The anticholinesterase eserine (10 μM) as well ACh-analog carbamylcholine chloride (CCh, 25 decreased amplitude duration evoked parallel, increased significantly rate occurrence discharges. These reversed muscarinic antagonist atropine (2.5 μM, n =20), but not nicotinic hexamethonium (50 =3). M1 subtype-selective pirenzepine (1 =12) blocked discharges 8/12 slices, while antagonists M2 (AFDX 116 =4), M3 (4-DAMP =4) M4 (gallamine =5, tropicamide =6) type, all at 1 only reduced their frequency. CCh-induced combination glutamate AP5 CNQX (both 10 μM; =11). Gap junction blockers abolished them (halothane, =7) or frequency 65% (carbenoxolone, =8). Inhibiting Ca 2+ release intracellular stores dantrolene (100 =5) thapsigargin also depressed frequencies 55–65%. By contrast, rates altered perfusion with high (7 mM; medium, a manipulation suppressing polysynaptic connections. findings demonstrate that activation receptors, notably neocortex facilitates glutamatergic are strongly inhibited gap blockers, partly mediated the, presumably receptor-dependent, mobilization calcium.