Chronic decentralization of the heart differentially remodels canine intrinsic cardiac neuron muscarinic receptors

Abstract

The objective of the study was to determine if chronic interruption of all extrinsic nerve inputs to the heart alters cholinergic-mediated responses within the intrinsic cardiac nervous system (ICN). Extracardiac nerve inputs to the ICN were surgically interrupted (ICN decentralized). Three weeks later, the intrinsic cardiac right atrial ganglionated plexus (RAGP) was removed and intrinsic cardiac neuronal responses were evaluated electrophysiologically. Cholinergic receptor abundance was evaluated using autoradiography. In sham controls and chronic decentralized ICN ganglia, neuronal postsynaptic responses were mediated by acetylcholine, acting at nicotinic and muscarinic receptors. Muscarine- but not nicotine-mediated synaptic responses that were enhanced after chronic ICN decentralization. After chronic decentralization, muscarine facilitation of orthodromic neuronal activation increased. Receptor autoradiography demonstrated that nicotinic and muscarinic receptor density associated with the RAGP was unaffected by decentralization and that muscarinic receptors were tenfold more abundant than nicotinic receptors in the right atrial ganglia in each group. After chronic decentralization of the ICN, intrinsic cardiac neurons remain viable and responsive to cholinergic synaptic inputs. Enhanced muscarinic responsiveness of intrinsic cardiac neurons occurs without changes in receptor abundance.

Dynamic remodeling of the guinea pig intrinsic cardiac plexus induced by chronic myocardial infarction

“…Muscarinic agonists exert major neuromodulating effects on IC neurons, and these effects can be altered in pathophysiological states (Bibevski and Dunlap, 2011; Dunlap et al, 2003; Smith et al, 2001). Bethanechol increased neuronal excitability over baseline levels following MI (Fig.…”

β1-Adrenoceptor blockade mitigates excessive norepinephrine release into cardiac interstitium in mitral regurgitation in dog

“…Labeling of ␤ 1-and ␤2-ARs in 20-m thick sections of unfixed LV myocardium was done by a modification of published protocols (14,20) using l-[ 125 I]iodocyanopindolol (PerkinElmer Life Sciences; Boston, MA), which is a membrane permeant ligand and measures both extracellular and intracellular receptors. Total binding was determined by incubation of sections for 90 min at 37°C in a Tris-salt buffer containing 0.1 nM [ 125 I]cyanopindolol, 10 M pargyline, and 10 M serotonin.…”

“…Incubation buffers for other sections also contained 3 M timolol (nonspecific binding) or 0.5 M CGP-20712A, a ␤ 1-AR antagonist. Radioligand binding sites were identified by film autoradiography and quantified by using a microcomputer-assisted imaging device (Imaging Research) as described previously (20). Total ␤-AR levels were calculated by subtracting nonspecific binding from total binding.…”

Local Innervation and Atrial Fibrillation

“…It is well demonstrated that increasing age drastically changes autonomic tone, perhaps in part due to the loss of autonomic neurons, reduced responsiveness to autonomic stimuli or a combination of the two. Smith et al demonstrated that even weeks after denervation of the ECNS, GP neurons remain fully viable and retain their ability to increase neurotransmitter release 48 . Thus, it is conceivable that as a person ages there may be an increased proclivity for AF owing to autonomously functioning GPs in the absence of strong autonomic tone.…”