Abstract
Whole-cell patch-clamp recordings were used to evaluate the effects of the cyclic nucleotides adenosine 3’,5’-cyclic monophosphate (cAMP) and guanosine 3’,5’-cyclic monophosphate (cGMP) on ionic currents in type I carotid body cells isolated from rat pups, and to investigate whether cyclic nucleotides are involved in K+ current inhibition by hypoxia. In the presence of 500 μM isobutylmethylxanthine, currents were not significantly modified by 8-bromo-cAMP (2 mM), dibutyryl-cAMP (5 mM) or 8-bromo-cGMP (2 mM). Currents were also unaffected by the phosphodiesterase (PDE)-resistant protein kinase A activators Sp-cyclic adenosine-3′,5′-monophosphorothioate (Sp-cAMPS) and Sp-8-bromoadenosine-3′,5′-monophosphorothioate (Sp-8-bromo-cAMPS) (50 μM), or by β-phenyl-1,N 2-ethenoguanosine-3′,5′-cyclic monophosphate (PET-cGMP) (100 μM) or the nitric oxide donor S-nitroso-N-acetylpenicillamine (SNAP; 500 μM). Ca2+ channel currents were also unaffected by Sp-8-Br-cAMPS, PET-cGMP and SNAP at the same concentrations. In the absence of cyclic nucleotide analogues, hypoxia (PO2 17–23 mmHg) reversibly inhibited K+ currents. This degree of hypoxic inhibition was not significantly altered by the PDE-resistant protein kinase A inhibitors Rp-cyclic adenosine-3′,5′-monophosphorothioate (Rp-cAMPS) (50 μM) or Rp-8-bromoadenosine-3′,5′-monophosphorothioate (Rp-8-bromo-cAMPS) (200 μM). Similarly, PET-cGMP (100 μM) and SNAP (500 μM) did not alter the degree of inhibition caused by hypoxia. At the same concentrations used in type I cell experiments, Sp-8-bromo-cAMPS, PET-cGMP and SNAP completely relaxed isolated guinea-pig basilar arteries preconstricted with 20 mM K+-containing solutions. Our results indicate that cyclic nucleotides alone are not an important factor in the regulation by O2 tension of K+ currents in rat type I carotid body cells.
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Received: 12 June 1996 / Accepted: 14 August 1996
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Hatton, C., Peers, C. Hypoxic inhibition of K+ currents in isolated rat type I carotid body cells: evidence against the involvement of cyclic nucleotides. Pfluegers Arch 433, 129–135 (1996). https://doi.org/10.1007/s004240050258
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DOI: https://doi.org/10.1007/s004240050258