M1 and M2 muscarinic receptors mediate excitation and inhibition of guinea-pig intracardiac neurones in culture.

摘要: 1. The effects of muscarine upon intracardiac neurones cultured from ganglia within the atria and interatrial septum newborn guinea-pig heart were studied using intracellular recording techniques. 2. Muscarine applied to neuronal soma typically produced a biphasic change in membrane potential which consisted small hyperpolarization followed by depolarization. In addition, (0.01-10 microM) inhibited calcium-dependent, after-hyperpolarization (AHP) greatly increased number action potentials that could be evoked given depolarizing current. 3. was associated with decrease input resistance it reversed become depolarization at -86.5 mV. This response antagonized 4-diphenylacetoxy-N-methyl-piperidine (4-DAMP; 100 nM) AF-DX 116 (500 nM), but unaffected pirenzepine (0.1-5 microM). 4. Two types slow observed presence muscarine. most common an increase range -70 -40 Pirenzepine (100 selectively this response, 4-DAMP similarly non-selective. (0.5-5 showed no antagonist effect. less (5% cells) had long latency resistance. 5. reduced duration AHP. Cadmium chloride mimicked these actions Application immediately following train did not inhibit AHP, suggesting directly calcium-activated potassium current (IK(Ca)). Muscarine-induced depression AHP either (0.1-0.5 or 6. It is concluded muscarine-induced results reduction conductance similar M-conductance, through activation M1 muscarinic receptors. conductance, M2