Selective inhibition of the Na + /H + exchanger type 3 activates CO 2 /H + -sensitive medullary neurones
作者： M. Wiemann , Jan-Robert Schwark , U. Bonnet , Hans Willi Jansen , Sergio Grinstein
关键词: Sodium–hydrogen antiporter 、 Hypercapnia 、 Hippocampal formation 、 Respiration 、 Medulla oblongata 、 Membrane potential 、 Biology 、 Neuroscience 、 Intracellular pH 、 Endocrinology 、 Internal medicine 、 Receptor 、 Clinical biochemistry 、 Physiology (medical) 、 Physiology
摘要: Hypercapnia as well lowered intracellular pH (pHi) increase the bioelectric activity of CO2/H+-sensitive neurones (VLNcs) ventrolateral medulla oblongata. Here we describe that immunoreactive Na+/H+ exchanger (NHE3) is present in from medullary organotypic cultures (obex level). To test whether VLNcs can be acidified and thereby activated by inhibition NHE3, used novel high-affinity NHE3-inhibitors S1611 S3226. Both drugs raised firing rates to at least 150% control values, depolarized membrane potential up 15 mV concentrations (0.5–1 µmol/l) suitable for selective NHE3. The changes strongly resembled responses hypercapnia (PCO2: 60–100 mmHg). In BCECF-AM-loaded a subfraction was found intracellularly 0.05–0.1 units following treatment with S1611; time course this acidification similar evoked hypercapnia. All drug effects were sustained readily reversible upon washing. Non-CO2/H+-responsive hippocampal CA3 unaffected 20 µmol/l S1611. It concluded NHE3 acidifies activates within
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