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Bondarenko, A; Sagach, V.
Na+-K+-ATPase is involved in the sustained ACh-induced hyperpolarization of endothelial cells from rat aorta.
Br J Pharmacol. 2006; 149(7):958-965
Doi: 10.1038/sj.bjp.0706913
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- Führende Autor*innen der Med Uni Graz
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Bondarenko Oleksandr
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- Abstract:
- Background and purpose. Inhibition of Na+-K+-ATPase is known to attenuate endothelium-dependent relaxation in many arteries. The purpose of this study was to evaluate the role of Na+-K+-ATPase in the regulation of endothelial membrane potential at rest and during stimulation by ACh. Experimental approach. Membrane potential was recorded from the endothelium of rat aorta using the perforated patch-clamp technique. Key results. Superfusion with K+-free solution produced a depolarization of about 11 mV from the resting value of -42.9 +/- 0.9 mV. Reintroduction of 4.7 mM K+ transiently hyperpolarized endothelial cells to -52.4 +/- 1.8 mV and the membrane potential recovered within 10 min. Ouabain 500 mM depolarized endothelium by about 11 mV and inhibited the hyperpolarization induced by K+ reintroduction into the K+-free solution. However, 500 nM ouabain did not affect the resting membrane potential or the hyperpolarization induced by K+ reintroduction. Pre-exposure to ouabain 500 mu M, but not 500 nM, attenuated the sustained component of hyperpolarization to ACh without affecting the amplitude of the transient peak hyperpolarization. In K+ free solution, the amplitude of peak hyperpolarization to ACh was increased, while the sustained component of hyperpolarization was attenuated. Conclusions and Implications. These results indicate that electrogenic Na+-K+-ATPase partially contributes to the sustained hyperpolarization of endothelial cells from rat aorta in response to ACh. They also suggest that the alpha 1, but not alpha 2 or alpha 3 isoforms, is involved in ACh-mediated hyperpolarization.
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Acetylcholine - pharmacology
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Animals -
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Aorta, Thoracic - cytology Aorta, Thoracic - drug effects Aorta, Thoracic - metabolism
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Calcium - metabolism
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Endothelial Cells - drug effects Endothelial Cells - metabolism
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Enzyme Inhibitors - pharmacology
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Ionomycin - pharmacology
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Membrane Potentials - drug effects
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Nitric Oxide Synthase - antagonists and inhibitors
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Ouabain - pharmacology
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Patch-Clamp Techniques -
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Potassium - metabolism
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Rats -
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Rats, Wistar -
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Sodium-Potassium-Exchanging ATPase - antagonists and inhibitors Sodium-Potassium-Exchanging ATPase - metabolism
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Time Factors -
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Vasodilator Agents - pharmacology
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omega-N-Methylarginine - pharmacology
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rat aorta
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endothelium
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membrane potential
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Na pump