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M1 and M2 muscarinic receptors mediate excitation and inhibition of guinea‐pig intracardiac neurones in culture.
Author(s) -
Allen T G,
Burnstock G
Publication year - 1990
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.1990.sp017995
Subject(s) - muscarine , depolarization , hyperpolarization (physics) , pirenzepine , muscarinic acetylcholine receptor , diastolic depolarization , reversal potential , chemistry , pacemaker potential , membrane potential , medicine , endocrinology , biophysics , electrophysiology , neuroscience , biology , receptor , biochemistry , stereochemistry , patch clamp , heart rate , sinoatrial node , nuclear magnetic resonance spectroscopy , blood pressure
1. The effects of muscarine upon intracardiac neurones cultured from ganglia within the atria and interatrial septum of the newborn guinea‐pig heart were studied using intracellular recording techniques. 2. Muscarine applied to the neuronal soma typically produced a biphasic change in membrane potential which consisted of a small hyperpolarization followed by a depolarization. In addition, muscarine (0.01‐10 microM) inhibited the calcium‐dependent, after‐hyperpolarization (AHP) and greatly increased the number of action potentials that could be evoked by a given depolarizing current. 3. The hyperpolarization was associated with a decrease in input resistance and it reversed to become a depolarization at a potential of ‐86.5 mV. This response was antagonized by 4‐diphenylacetoxy‐N‐methyl‐piperidine (4‐DAMP; 100 nM) and AF‐DX 116 (500 nM), but was unaffected by pirenzepine (0.1‐5 microM). 4. Two types of slow depolarization were observed in the presence of muscarine. The most common was associated with an increase in input resistance in the potential range ‐70 to ‐40 mV. Pirenzepine (100 nM) selectively antagonized this response, 4‐DAMP (100 nM) similarly antagonized the response, but was non‐selective. AF‐DX 116 (0.5‐5 microM) showed no antagonist effect. The less common depolarization (5% of cells) had a long latency and was associated with a decrease in input resistance. 5. Muscarine reduced the duration of the action potential and inhibited the AHP. Cadmium chloride (100 microM) mimicked these actions of muscarine. Application of muscarine immediately following a train of action potentials did not inhibit the AHP, suggesting that muscarine did not directly inhibit the calcium‐activated potassium current (IK(Ca)). Muscarine‐induced depression of the slow AHP was antagonized by 4‐DAMP (100 nM) but was not antagonized by either pirenzepine (0.1‐0.5 microM) or AF‐DX 116 (0.5‐5 microM). 6. It is concluded that the muscarine‐induced depolarization of guinea‐pig intracardiac neurones results from reduction of a potassium conductance similar to the M‐conductance, through activation of M1 muscarinic receptors. The hyperpolarization results from an increase in potassium conductance, through activation of M2 muscarinic receptors.