Persistent muscarinic excitation in guinea-pig olfactory cortex neurons: involvement of a slow post-stimulus afterdepolarizing current.
The persistent excitatory effects of the muscarinic agonist oxotremorine-M were investigated in guinea-pig olfactory cortex neurons in vitro (28-30 degrees C) using a single-microelectrode current-clamp/voltage-clamp technique. In 40% of recorded cells (type 1), bath-application of oxotremorine-M (2-10 microM; 1-2 min) induced a strong membrane depolarization, an increase in input resistance and a sustained neuronal discharge lasting over 30 min following agonist washout. A large depolarizing stimulus applied during the action of oxotremorine-M, evoked a slow post-stimulus afterdepolarization (approximately 10-15 mV) lasting approximately 30 s. Injection of steady negative current at the peak of this response produced a slow repolarization of the membrane potential (half-time approximately 0.6 min) towards a plateau level ("hyperpolarization recovery"); these effects of oxotremorine-M were slowly reversed on washout or by application of atropine (1 microM). In a second population of neurons (type 2; 39% of total), oxotremorine-M produced a large depolarization, a resistance increase and repetitive firing that did not persist after agonist washout; these neurons failed to generate a prominent slow afterdepolarization on stimulation, and showed no hyperpolarization recovery effect. Their resting membrane properties were not significantly different from those of type 1 cells. The remaining proportion of cells (type 3) elicited little or no muscarinic response to oxotremorine-M and no slow afterdepolarization; these cells showed characteristics spike fractionation (pre-potentials) during an evoked train of action potentials.(ABSTRACT TRUNCATED AT 250 WORDS)
Constanti
A
A
Department of Pharmacology, School of Pharmacy, London.
Bagetta
G
G
Libri
V
V
D015761:4-Aminopyridine / Q000494:pharmacology; D000200:Action Potentials; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001464:Barium / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D006168:Guinea Pigs; D007811:Lanthanum / Q000494:pharmacology; D008564:Membrane Potentials; D009474:Neurons / Q000737:chemistry / Q000502:physiology; D009833:Olfactory Pathways / Q000737:chemistry / Q000502:physiology*; D010095:Oxotremorine / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000502:physiology; D014403:Tubocurarine / Q000494:pharmacology
D015221:Potassium Channels; D000644:Quaternary Ammonium Compounds; D011976:Receptors, Muscarinic; D001464:Barium; D010095:Oxotremorine; D007811:Lanthanum; D001285:Atropine; D015761:4-Aminopyridine; C009405:tetrabutylammonium; D005905:Glyburide; D014403:Tubocurarine