Acetylcholine receptors in rat cardiac neurones

doi:10.1016/0165-1838(92)90223-4

Journal of the Autonomic Nervous System

Volume 40, Issue 1, August 1992, Pages 33-47

Journal of the Auton...

https://doi.org/10.1016/0165-1838(92)90223-4 Get rights and content

Abstract

Membrane potential changes produced by acetylcholine (ACh), and their underlying mechanisms, were studied in neurones of isolated cardiac ganglia of the rat by means of intracellular microelectrodes. Five components of membrane potential change could be detected in cardiac neurones following 1–5 s micro-application of ACh; (i) fast depolarization resulting from an activation of nonselective cationic conductance; (ii) slow depolarization associated with a decreased membrane conductance, presumably for potassium ions; slow hyperpolarization which consisted of (iii) early and (iv) late parts resulting from an activation of calcium-sensitive potassium current and from inhibition of steady-state inward current, respectively; and (v) delayed slow hyperpolarization associated with an increased conductance, most likely for potassium ions. Components (i), (iii) and (iv) persisted in the presence of atropine and were inhibited by nicotinic antagonists. Thus they were due to activation of nicotinic ACh receptors. However, the sensitivity of component (i) to ganglion-blocking agents appeared to be rather low: IC₅₀s for inhibiting (i) were 226 ± 34.2 μM, 31.2 ± 4.31 μM and 15.3 ± 3.27 μM for hexamethonium, d-tubocurarine, and trimetaphan, respectively. Components (ii) and (v) were abolished by atropine (1 μM) and mimicked by muscarine (component (ii) also persisted in d-tubocurarine), hence they resulted from activation of muscarinic ACh receptors. It is concluded that cardiac neurones are endowed with both nicotinic and muscarinic ACh receptors. Their activation leads to membrane depolarization and discharges followed by hyperpolarization and inhibition of discharges.

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1993, Pharmacology and Therapeutics
At least five muscarinic receptors genes have been cloned and expressed. Muscarinic receptors act via activation of G proteins: m1, m3 and m5 muscarinic receptors couple to stimulate phospholipase C, while m2 and m4 muscarinic receptors inhibit adenylyl cyclase. This review describes the localization, pharmacology and function of the five muscarinic receptor subtypes. The actions of muscarinic receptors on the heart, smooth muscle, glands and on neurons (both presynaptic and postsynaptic) in the autonomic nervous system and the central nervous system are analyzed in terms of subtypes, biochemical mechanisms and effects on ion channels, including K⁺ channels and Ca²⁺ channels.
Membrane properties and firing characteristics of rat cardiac neurones in vitro
1992, Journal of the Autonomic Nervous System
Electrophysiological characteristics of neurones in isolated cardiac ganglia from the left atrium and interatrial septum of the rat were studied with intracellular microelectrodes. At rest the neurones were characterized by a membrane potential of − 52.6 ± 0.83 mV, an input resistance of $85.6 ± 7.6 M Ω$ , a membrane time constant of 4.6 ± 0.24 ms and an input capacitance of 63.1 ± 5.25 pF. Removal of Ca²⁺ ions from the external solution resulted in a membrane depolarisation of 5.5 ± 0.70 mV and an increase in input resistance of 96 ± 52% which indicated that a substantial Ca²⁺-sensitive component contributed to resting membrane potential. A prolonged after-hyperpolarization (AHP) was recorded following a train of spikes; this was inhibited in a Ca²⁺-free solution, indicating that a Ca²⁺-sensitive component of potassium conductance contributed to it. On the basis of the duration of the AHP following a single spike, two types of neurones, I and II, were tentatively identified, having short (< 300 ms) and long (> 300 ms) AHPs, respectively. Type I neurones responded to prolonged membrane depolarization with bursts of firing (I_b neurones) or multiple discharges (I_m neurones). Type II neurones also responded with single spikes or multiple discharges to prolonged membrane depolarization. In some I_m neurones, tonic firing was recorded which was inhibited by a hyperpolarizing current and accelerated by a depolarizing current injected through the recording microelectrode. Thus, neurones of isolated cardiac ganglia of the rat from the region studied here are heterogeneous in their electrical behaviour, suggesting the existence of functionally different groups within the ganglia.
Synaptic transmission in rat cardiac neurones
1992, Journal of the Autonomic Nervous System
Intracellular recordings of spontaneous synaptic activity and synaptic responses to fibre tract stimulation were taken from neurones of ganglia isolated from the left atrium and interatrial septum of the rat. In six out of 57 neurones studied, spontaneous fast excitatory postsynaptic potentials (EPSPs) were recorded. Single stimulation of fibre tracts approaching the ganglion resulted in an all-or-none response consisting of an EPSP, from which an action potential abruptly appeared. This response disappeared in Ca²⁺-free/high-Mg²⁺ solution, indicating that it was orthodromic in origin. EPSPs were markedly exaggerated and prolonged by neostigmine (1–5 μM). EPSPs produced by high-frequency (0.1–20 Hz) fibre tract stimulation were markedly attenuated when compared with responses to single fibre tract stimulation, although they usually remained suprathreshold for spike initiation. High concentrations of hexamethonium (1 mM) and d-tubocurarine (300 μM) failed to inhibit responses to single fibre tract stimulation, although they completely abolished responses to high-frequency stimulation. Responses to single fibre tract stimulation were abolished by trimetaphan (≥ 100 μM). No slow synaptic responses were detected during single or high-frequency fibre tract stimulation. All cardiac neurones that responded orthodromically were highly excitable: they had a short post-spike after-hyperpolarization (AHP) and responded with multiple firing to prolonged membrane depolarization. It is concluded that cardiac neurones, in the region of the heart studied here, receive single ‘strong’ cholinergic inputs from some fibre tracts approaching the ganglion that elicit EPSPs accompanied by spikes. EPSPs are rather resistant to ganglion-blocking agents and subject to frequency modulation.
Non-quantal release of acetylcholine from parasympathetic nerve terminals in the right atrium of rats: Experimental Physiology-Research Paper
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Research paperAcetylcholine receptors in rat cardiac neurones

Abstract

Neurosci. Lett.

J. Auton. Nerv. Syst.

Life Sci.

Eur. J. Pharmacol.

Neuroscience

Brain Res.

Brain Res.

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

J. Physiol. (Lond.)

Function of the heart

M currents

Two components of muscarine-sensitive membrane current in rat sympathetic neurones

J. Physiol. (Lond.)

Origin of the after-hyperpolarization that follows removal of depolarizing agents from the isolated superior cervical ganglion of the rat

Br. J. Pharmacol.

M-currents in voltage-clamped mammalian sympathetic neurones

Neurosci. Lett.

Inhibition and facilitation in parasympathetic ganglia of the urinary bladder

Synaptic transmission and its duplication by focally applied acetylcholine in parasympathetic neurons in the heart of the frog

Muscarinic inhibition of sympathetic C neurones in the bullfrog

J. Physiol. (Lond.)

The interaction of hexamethonium with muscarinic receptor subtype in vitro

Br. J. Pharmacol.

Research paper
Acetylcholine receptors in rat cardiac neurones

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