Functional expression of the α7 and α4-containing nicotinic acetylcholine receptors on the neonatal rat carotid body
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Date
2012
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Abstract
The carotid bodies (CBs) are chemosensory organs that respond to hypoxemia with transmitter neurosecretion, leading to a respiratory reflex response. It has been proposed that acetylcholine is a key regulator of transmitter release through activation of presynaptic nicotinic acetylcholine receptors (nAChRs). In the present work, we studied the identity of such nAChRs and their contribution to catecholamine release from CBs.
Neonatal rat CBs were placed in a recording chamber for electrochemical recordings or disassociated for voltage-clamp studies on isolated cells. Fast nicotine superfusion increases catecholamine release from intact CBs. This response was diminished reversibly by the non-selective nAChR blocker hexamethonium, by the selective alpha 7 blocker alpha-bungarotoxin and by the alpha 4-containing nAChR blocker erysodine.
In isolated CB cells the nAChR agonists nicotine, acetylcholine and cytisine all evoke inward currents with similar potencies. The nicotine-evoked current was fully blocked by mecamylamine and partially inhibited by alpha-bungarotoxin or erysodine. However, the combination of both alpha-bungarotoxin an erysodine failed to suppress this response. Immunodetection studies confirm the presence of alpha 7 and alpha 4 subunits in isolated dopaminergic CB cells. Our results show that activation of alpha 7 and/or alpha 4-containing nAChR subtypes have the ability to regulate catecholamine release from intact CB due to activation of fast inward currents expressed in chemoreceptor cells. Therefore, our results suggest that both nAChR subtypes contribute to the cholinergic nicotinic regulation of catecholamine signaling in the carotid body system. (C) 2011 Elsevier Ltd. All rights reserved.
Neonatal rat CBs were placed in a recording chamber for electrochemical recordings or disassociated for voltage-clamp studies on isolated cells. Fast nicotine superfusion increases catecholamine release from intact CBs. This response was diminished reversibly by the non-selective nAChR blocker hexamethonium, by the selective alpha 7 blocker alpha-bungarotoxin and by the alpha 4-containing nAChR blocker erysodine.
In isolated CB cells the nAChR agonists nicotine, acetylcholine and cytisine all evoke inward currents with similar potencies. The nicotine-evoked current was fully blocked by mecamylamine and partially inhibited by alpha-bungarotoxin or erysodine. However, the combination of both alpha-bungarotoxin an erysodine failed to suppress this response. Immunodetection studies confirm the presence of alpha 7 and alpha 4 subunits in isolated dopaminergic CB cells. Our results show that activation of alpha 7 and/or alpha 4-containing nAChR subtypes have the ability to regulate catecholamine release from intact CB due to activation of fast inward currents expressed in chemoreceptor cells. Therefore, our results suggest that both nAChR subtypes contribute to the cholinergic nicotinic regulation of catecholamine signaling in the carotid body system. (C) 2011 Elsevier Ltd. All rights reserved.
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Keywords
Carotid body, Acetylcholine, Nicotinic acetylcholine receptors, Catecholamines