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Co‐release of ATP and ACh mediates hypoxic signalling at rat carotid body chemoreceptors
Author(s) -
Zhang Min,
Zhong Huijun,
Vollmer Cathy,
Nurse Colin A.
Publication year - 2000
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 - 10.1111/j.1469-7793.2000.t01-1-00143.x
Subject(s) - carotid body , medicine , endocrinology , excitatory postsynaptic potential , suramin , chemistry , postsynaptic potential , mecamylamine , acetylcholine , neurotransmission , ppads , purinergic receptor , electrophysiology , biology , nicotinic agonist , inhibitory postsynaptic potential , adenosine , receptor
1 Using functional co‐cultures of rat carotid body (CB) O 2 chemoreceptors and ‘juxtaposed’ petrosal neurones (JPNs), we tested whether ATP and ACh acted as co‐transmitters. 2 Perforated‐patch recordings from JPNs often revealed spontaneous and hypoxia‐evoked ( P O2 ≈5 mmHg) excitatory postsynaptic responses. The P2X purinoceptor blocker, suramin (50 μM) or a nicotinic ACh receptor (nAChR) blocker (hexamethonium, 100 μM; mecamylamine, 1 μM) only partially inhibited these responses, but together, blocked almost all activity. 3 Under voltage clamp (‐60 mV), fast perfusion of 100 μM ATP over hypoxia‐responsive JPNs induced suramin‐sensitive (IC 50 = 73 μM), slowly‐desensitizing, inward currents ( I ATP ) with time constant of activation τ on = 30.6 ± 4.8 ms ( n = 7 ). I ATP reversed at 0.33 ± 3.7 mV ( n = 4 ), and the dose‐response curve was fitted by the Hill equation (EC 50 = 2.7 μM; Hill coefficient ≈0.9). These purinoceptors contained immunoreactive P2X 2 subunits, but their activation by α,β‐methylene ATP (α,β‐meATP; EC 50 = 2.1 μM) suggests they are P2X 2 /P2X 3 heteromultimers. 4 Suramin and nAChR blockers inhibited the extracellular chemosensory discharge in the intact rat carotid body‐sinus nerve preparation in vitro. Further, P2X 2 immunoreactivity was widespread in rat petrosal ganglia in situ , and co‐localized in neurones expressing the CB chemo‐afferent marker, tyrosine hydroxylase (TH). P2X 2 labelling in the CB co‐localized with nerve‐terminal markers, and was intimately associated with TH‐positive type 1 cells. 5 Thus ATP and ACh are co‐transmitters during chemotransduction in the rat carotid body.