A possible dual site of action for carbon monoxide-mediated chemoexcitation in the rat carotid body

Christine Barbe, Fahaid Al Hashem, Anneli Conway, E Dubuis, C Vandier, Prem Kumar

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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 muM). Addition of the P-2 purinoceptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (50 muM) 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.
Original languageEnglish
Pages (from-to)933-945
Number of pages13
JournalThe Journal of Physiology
Early online date26 Jul 2002
Publication statusPublished - 15 Sept 2002


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