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Co-release of ATP and ACh mediates hypoxic signalling at rat carotid body chemoreceptors

Min Zhang, Huijun Zhong, Cathy Vollmer and Colin A. Nurse

1. Using functional co-cultures of rat carotid body (CB) O₂ 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 (IC₅₀ = 73 µM), slowly-desensitizing, inward currents (I_ATP) with time constant of activation _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 (EC₅₀ = 2·7 µM; Hill coefficient ~0·9). These purinoceptors contained immunoreactive P2X₂ subunits, but their activation by ,-methylene ATP (,-meATP; EC₅₀ = 2·1 µM) suggests they are P2X₂/P2X₃ heteromultimers.

4. Suramin and nAChR blockers inhibited the extracellular chemosensory discharge in the intact rat carotid body-sinus nerve preparation in vitro. Further, P2X₂ immunoreactivity was widespread in rat petrosal ganglia in situ, and co-localized in neurones expressing the CB chemo-afferent marker, tyrosine hydroxylase (TH). P2X₂ 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.

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