1. Plasma adenosine concentration increases during hypoxia to a level that excites carotid body chemoreceptors by an undetermined mechanism. We have examined this further by determining the electrophysiological responses to exogenous adenosine of sinus nerve chemoafferents in vitro and of whole-cell currents in isolated type I cells. 2. Steady-state, single-fibre chemoafferent discharge was increased approximately 5-fold above basal levels by 100 ìÒ adenosine. This adenosine-stimulated discharge was reversibly and increasingly reduced by methoxyverapamil (D600, 100 ìÒ), by application of nickel chloride (Ni¥, 2 mÒ) and by removal of extracellular Ca¥. These effects strongly suggest a presynaptic, excitatory action of adenosine on type I cells of the carotid body. 3. Adenosine decreased whole-cell outward currents at membrane potentials above -40 mV in isolated type I cells recorded during superfusion with bicarbonate-buffered saline solution at 34-36°C. This effect was reversible and concentration dependent with a maximal effect at 10 ìÒ. 4. The degree of current inhibition induced by 10 ìÒ adenosine was voltage independent (45•39 ± 2•55 % (mean ± s.e.m.) between −40 and +30 mV) and largely (•75%), but not entirely, Ca¥ independent. 4-Aminopyridine (4-AP, 5 mÒ) decreased the amplitude of the control outward current by 80•60 ± 3•67 % and abolished the effect of adenosine. 5. Adenosine was without effect upon currents near the resting membrane potential of approximately −55 mV and did not induce depolarization in current-clamp experiments. 6. We conclude that adenosine acts to inhibit a 4-AP-sensitive current in isolated type I cells of the rat carotid body and suggest that this mechanism contributes to the chemoexcitatory effect of adenosine in the whole carotid body.

High tensions of carbon monoxide (CO), relative to oxygen, were used as a tool to investigate the mechanism of chemotransduction. In an in vitro whole organ, rat carotid body preparation, CO increased sinus nerve chemoafferent discharge in the dark, an effect that was significantly reduced (by ca 70 %) by bright white light and by the removal of extracellular Ca2+ from the superfusate or by the addition of either Ni2+ (2 mM) or methoxyverapamil (100 μM). Addition of the P2 purinoceptor antagonist pyridoxalphosphate‐6‐azophenyl‐2′,4′‐disulphonic acid (50 μM) also significantly reduced the neural response to CO. In perforated patch, whole‐cell recordings of isolated rat type I cells, CO induced a depolarisation of ca 11 mV and a decrease in the amplitude of an outward current around and above the resting membrane potential. Membrane conductance between ‐50 and ‐60 mV was significantly reduced by ca 40 % by CO. These effects were not photolabile and were present also when a ‘blocking solution’ containing TEA, 4‐AP, Ni2+ and zero extracellular Ca2+ was used. In conventional whole‐cell recordings, CO only decreased current amplitudes above +10 mV and was without effect around the resting membrane potential. These data demonstrate a direct effect of CO upon type I cell K+ conductances and strongly suggest an effect upon a background, leak conductance that requires an intracellular mediator. The photolabile effect of CO only upon afferent neural discharge adds further evidence to a dual site of action of CO with a separate action at the afferent nerve terminal that, additionally, requires the permissive action of the neurotransmitter ATP.

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