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C Peers

Publications and source records attributed to C Peers.

115 records · Page 7Linked to original sources
PubMed1989

Tolbutamide reverses hypoxic pulmonary vasoconstriction in isolated rat lungs.

We have investigated the effects of tolbutamide on the hypoxic vasoconstriction of isolated, perfused rat lungs. We did this because lowered ATP may link hypoxia and constriction, and tolbutamide mimics the effects of ATP in other tissues by blocking ATP-sensitive potassium (ATP-K) channels. Pulmonary vasoconstriction, induced by lowering the oxygen of the gas ventilating the lungs from 95 to 2%, was always reduced or abolished by tolbutamide (1.7 x 10(-4)-8.5 x 10(-3) M). High concentrations (greater than or equal to 10(-3) M) of diazoxide, a drug that opens ATP-K channels, dramatically constricted the pulmonary vasculature and this effect was also reversed by tolbutamide. The opening of ATP-K channels may therefore underlie hypoxic pulmonary vasoconstriction.

Adenosine Triphosphate↗
PubMed1987

The effect of myasthenic syndrome antibody on presynaptic calcium channels in the mouse.

1. The action of immunoglobulin G obtained from patients with Lambert-Eaton myasthenic syndrome (LEMS IgG) was investigated by injecting mice, followed by intracellular recordings from the mouse diaphragm. 2. End-plate potential quantal content was studied over a range of Ca2+ concentrations. Curves of log quantal content versus log Ca2+ concentration were shifted to the right by LEMS IgG. For low Ca2+ concentrations, release continued to follow Poisson statistics after LEMS IgG treatment. 3. Miniature end-plate potential (m.e.p.p.) frequency was measured in solutions containing high K+ concentrations. LEMS IgG significantly reduced m.e.p.p. frequency at each K+ concentration studied. 4. M.e.p.p. frequency was measured at fixed high-K+ concentration (15.9 mM) for a range of Ca2+ concentrations. The log-log plot of m.e.p.p. frequency versus Ca2+ concentration was shifted downwards throughout by LEMS IgG. 5. M.e.p.p. frequency was not affected by LEMS IgG in Ca2+-free solutions (K+ concentration 15.9 mM) or in solutions of low Ca2+ concentration (K+ concentration 5.9 mM). 6. At each Ca2+ concentration studied, m.e.p.p. amplitudes were not affected by LEMS IgG. 7. The data suggest that LEMS IgG acts on presynaptic voltage-dependent Ca2+ channels to cause their loss of function, probably by down-regulation.

Action Potentials↗
PubMedDate not supplied

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 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.

Animals↗
PubMedDate not supplied

Regulation of recombinant human brain tandem P domain K+ channels by hypoxia: a role for O2 in the control of neuronal excitability?

The tandem P domain potassium channels, TREK1 and TASK1, are expressed throughout the brain but expression patterns do not significantly overlap. Since normal pO2 in central nervous tissue is as low as 20 mmHg and can decrease even further in ischemic disease, it is important that the behaviour of human brain ion channels is studied under conditions of acute and chronic hypoxia. This is especially true for brain-expressed tandem P-domain channels principally because they are important contributors to neuronal resting membrane potential and excitability. Here, we discuss some recent data derived from two recombinant tandem P-domain potassium channels, hTREK1 and hTASK1. Hypoxia represents a potent inhibitory influence on both channel types and occludes the activation by arachidonic acid, intracellular acidosis and membrane deformation of TREK1. This casts doubt on the idea that TREK1 activation during brain ischemia might facilitate neuroprotection via hyperpolarising neurons in which it is expressed. Interestingly, hypoxia is unable to regulate alkalotic inhibition of TREK1 suggesting that this channel may be more intimately involved in control of excitability during physiological or pathological alkalosis.

Arachidonic Acid↗