Identification of M1 and M2 muscarinic acetylcholine receptors in the cat carotid body chemosensory system

Shirahata, Machiko; Hirasawa, Soichiro; Okumura, Mariko; Mendoza, Jeffrey A.; Okumura, Atsushi; Balbir, Alexander; Fitzgerald, Robert S.

doi:10.1016/j.neuroscience.2004.06.068

Cited by 20 publications

(7 citation statements)

References 31 publications

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“…Since the cat GCs also contain muscarinic receptors (M1 and M2; Shirahata, et al 2004), atropine was used to test a possible muscarinic role for ADO. Figure 10A presents the protocol for this type of superfusion.…”

Section: Resultsmentioning

confidence: 99%

The impact of adenosine and an A2A adenosine receptor agonist on the ACh-induced increase in intracellular calcium of the glomus cells of the cat carotid body

2009

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The carotid body (CB) is a polymodal chemosensor of arterial blood located next to the internal carotid artery. The basic chemosensing unit is composed of the neurotransmitter (NT)-containing glomus cells (GCs) and the sensory afferent fibers synapsing onto the GCs. Nicotinic and muscarinic receptors have been found on both the sensory afferent fibers and on the GCs. Neural output from the CB (CBNO) increases when arterial blood perfusing it is hypoxic, hypoglycemic, hypercapnic, or acidic. The increased CBNO due to GC release of excitatory NTs must be preceded by an entrance of calcium into the GCs. With repeated release of ACh from the GCs, cholinergic receptors could become desensitized, particularly nicotinic receptors which function as calcium channels. The purpose of the present study was to see if adenosine (ADO), known to alter receptor sensitivities, could attenuate or eliminate any desensitization of the nicotinic receptors occurring during the repeated application of ACh. Cat CBs were harvested with techniques approved by the University's Animal Care/Use Committee. The GCs were cultured and prepared for detecting [Ca ++ ] i with standard techniques. Repeated application of ACh produced a progressively decreasing increase in [Ca ++ ] i . With the use of ADO or an A2A ADO receptor agonist the decrease was avoided. Though ADO also increased GC [Ca ++ ] i , the sum of ADO increase and ACh increase, when superfused separately, was less than the increase when they were both included in the same superfusion. This suggested the possible involvement of a new path in the action. Potential mechanisms to explain the phenomena are discussed.

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Section: Resultsmentioning

confidence: 99%

The impact of adenosine and an A2A adenosine receptor agonist on the ACh-induced increase in intracellular calcium of the glomus cells of the cat carotid body

2009

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“…Acetylcholine through nicotinic receptors generally increases activity in the chemoreceptor afferents while the role of muscarinic receptors is less clear although they appear to modulate the nicotinic response in carotid body (for review, Iturriaga and Alcayaga, 2004). Shirahata et al (2004) reported the presence of M1 muscarinic acetylcholine receptors on the nerve terminals in the carotid body of cat.…”

Section: Discussionmentioning

confidence: 99%

Distribution of voltage‐gated potassium and hyperpolarization‐activated channels in sensory afferent fibers in the rat carotid body

Buniel

Glazebrook

Ramirez‐Navarro

et al. 2008

J of Comparative Neurology

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The chemosensory glomus cells of the carotid body (CB) detect changes in O2-tension. Carotid sinus nerve fibers, which originate from peripheral sensory neurons located within the petrosal ganglion, innervate the CB. Release of transmitter from glomus cells activates the sensory afferent fibers to transmit information to the nucleus of the solitary tract in the brainstem. The ion channels expressed within the sensory nerve terminals play an essential role in the ability of the terminal to initiate action potentials in response to transmitter-evoked depolarization. However, with a few exceptions, the identity of ion channels expressed in these peripheral nerve fibers is unknown. This study addresses the expression of voltage-gated channels in the sensory fibers with a focus on channels that set the resting membrane potential and regulate discharge patterns. Using immunohistochemistry and fluorescence confocal microscopy, potassium channel subunits and HCN (hyperpolarization-activated) family members were localized both in petrosal neurons that expressed tyrosine hydroxylase, and the CSN axons within the carotid body. Channels contributing to resting membrane potential including HCN2, responsible in part for Ih current, and the KCNQ2 and KCNQ5 subunits thought to underlie the neuronal “M current” were identified in the sensory neurons and their axons innervating the carotid body. In addition, the results presented here demonstrate expression of several potassium channels that shape the action potential and the frequency of discharge including Kv1.4, Kv1.5, Kv4.3, KCa (BK). The role of these channels should be considered in interpretation of the fiber discharge in response to perturbation of the carotid body environment.

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“…Acetylcholine is one of the main transmitters within the carotid body that robustly increases intracellular calcium in rat glomus cells (177). The carotid body expresses both nicotinic and muscarinic M1 and M2 receptors in rats (107) and cats (151). Immunohistological studies in rats suggest that the larger type A glomus cells are devoid of nicotinic receptors, which are found preferentially on smaller type B cells (18,20).…”

Section: Acetylcholinementioning

confidence: 99%

The Logic of Carotid Body Connectivity to the Brain

et al. 2019

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The carotid body has emerged as a therapeutic target for cardio-respiratory-metabolic diseases. With the expansive functions of the chemoreflex, we sought mechanisms to explain differential control of individual responses. We purport a remarkable correlation between phenotype of a chemosensory unit (glomus cell-sensory afferent) with a distinct component of the reflex response. This logic could permit differential modulation of distinct chemoreflex responses, a strategy ideal for therapeutic exploitation.

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Identification of M1 and M2 muscarinic acetylcholine receptors in the cat carotid body chemosensory system

Cited by 20 publications

References 31 publications

The impact of adenosine and an A2A adenosine receptor agonist on the ACh-induced increase in intracellular calcium of the glomus cells of the cat carotid body

The impact of adenosine and an A2A adenosine receptor agonist on the ACh-induced increase in intracellular calcium of the glomus cells of the cat carotid body

Distribution of voltage‐gated potassium and hyperpolarization‐activated channels in sensory afferent fibers in the rat carotid body

The Logic of Carotid Body Connectivity to the Brain

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