Effects of hypoxia, anoxia, and metabolic inhibitors on KATP channels in rat femoral artery myocytes
| Autor: | Helen E. Burrell, John M. Quayle, Tomoko Kamishima, Malcolm R Turner |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Male
Potassium Channels Physiology Calcium in biology Muscle Smooth Vascular Rats Sprague-Dawley chemistry.chemical_compound Adenosine Triphosphate Physiology (medical) Animals Glycolysis Cells Cultured Membrane potential ATP synthase biology Voltage-dependent calcium channel Potassium channel Cell Hypoxia Cell biology Rats Femoral Artery Oxygen Vasodilation chemistry Biochemistry biology.protein Cats Potassium Calcium Calcium Channels Cardiology and Cardiovascular Medicine Energy Metabolism Adenosine triphosphate Ion Channel Gating Intracellular Muscle Contraction |
| Zdroj: | American journal of physiology. Heart and circulatory physiology. 291(1) |
| ISSN: | 0363-6135 |
| Popis: | Vascular ATP-sensitive potassium (KATP) channels have an important role in hypoxic vasodilation. Because KATP channel activity depends on intracellular nucleotide concentration, one hypothesis is that hypoxia activates channels by reducing cellular ATP production. However, this has not been rigorously tested. In this study we measured KATP current in response to hypoxia and modulators of cellular metabolism in single smooth muscle cells from the rat femoral artery by using the whole cell patch-clamp technique. KATP current was not activated by exposure of cells to hypoxic solutions (Po2 ∼35 mmHg). In contrast, voltage-dependent calcium current and the depolarization-induced rise in intracellular calcium concentration ([Ca2+]i) was inhibited by hypoxia. Blocking mitochondrial ATP production by using the ATP synthase inhibitor oligomycin B (3 μM) did not activate current. Blocking glycolytic ATP production by using 2-deoxy-d-glucose (5 mM) also did not activate current. The protonophore carbonyl cyanide m-chlorophenylhydrazone (1 μM) depolarized the mitochondrial membrane potential and activated KATP current. This activation was reversed by oligomycin B, suggesting it occurred as a consequence of mitochondrial ATP consumption by ATP synthase working in reverse mode. Finally, anoxia induced by dithionite (0.5 mM) also depolarized the mitochondrial membrane potential and activated KATP current. Our data show that: 1) anoxia but not hypoxia activates KATP current in femoral artery myocytes; and 2) inhibition of cellular energy production is insufficient to activate KATP current and that energy consumption is required for current activation. These results suggest that vascular KATP channels are not activated during hypoxia via changes in cell metabolism. Furthermore, part of the relaxant effect of hypoxia on rat femoral artery may be mediated by changes in [Ca2+]i through modulation of calcium channel activity. |
| Databáze: | OpenAIRE |
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