Hypoxic inhibition of K+ currents in isolated rat type I carotid body cells: evidence against the involvement of cyclic nucleotides
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 whet...
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Veröffentlicht in: | Pflügers Archiv 1996-11, Vol.433 (1-2), p.129-135 |
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Zusammenfassung: | 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 microM 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 microM), or by beta-phenyl-1,N2-ethenoguanosine-3',5'-cyclic monophosphate (PET-cGMP) (100 microM) or the nitric oxide donor S-nitroso-N-acetylpenicillamine (SNAP; 500 microM). 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 microM) or Rp-8-bromoadenosine-3',5'-monophosphorothioate (Rp-8-bromo-cAMPS) (200 microM). Similarly, PET-cGMP (100 microM) and SNAP (500 microM) 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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ISSN: | 0031-6768 1432-2013 |
DOI: | 10.1007/s004240050258 |