Frequency modulation of Ca2+ sparks is involved in regulation of arterial diameter by cyclic nucleotides
| Autor: | Andra S. Stevenson, Thomas Kleppisch, Adrian D. Bonev, Valerie A. Porter, Mark T. Nelson, Harm J. Knot, W. J. Lederer, Thomas J. Heppner |
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| Rok vydání: | 1998 |
| Předmět: |
Niacinamide
Nitroprusside medicine.medical_specialty Potassium Channels Physiology Vasodilator Agents chemistry.chemical_element Vasodilation Calcium In Vitro Techniques chemistry.chemical_compound Internal medicine medicine Myocyte Animals Nucleotide Nicorandil chemistry.chemical_classification Forskolin Colforsin Electric Conductivity Cell Biology Arteries Cerebral Arteries Coronary Vessels Rats Vasomotor System Endocrinology chemistry Sodium nitroprusside Signal transduction Nucleotides Cyclic medicine.drug |
| Zdroj: | The American journal of physiology. 274(5) |
| ISSN: | 0002-9513 |
| Popis: | Forskolin, which elevates cAMP levels, and sodium nitroprusside (SNP) and nicorandil, which elevate cGMP levels, increased, by two- to threefold, the frequency of subcellular Ca2+release (“Ca2+sparks”) through ryanodine-sensitive Ca2+release (RyR) channels in the sarcoplasmic reticulum (SR) of myocytes isolated from cerebral and coronary arteries of rats. Forskolin, SNP, nicorandil, dibutyryl-cAMP, and adenosine increased the frequency of Ca2+-sensitive K+(KCa) currents [“spontaneous transient outward currents” (STOCs)] by two- to threefold, consistent with Ca2+sparks activating STOCs. These agents also increased the mean amplitude of STOCs by 1.3-fold, an effect that could be explained by activation of KCachannels, independent of effects on Ca2+sparks. To test the hypothesis that cAMP could act to dilate arteries through activation of the Ca2+spark→KCachannel pathway, the effects of blockers of KCachannels (iberiotoxin) and of Ca2+sparks (ryanodine) on forskolin-induced dilations of pressurized cerebral arteries were examined. Forskolin-induced dilations were partially inhibited by iberiotoxin and ryanodine (with no additive effects) and were entirely prevented by elevating external K+. Forskolin lowered average Ca2+in pressurized arteries while increasing ryanodine-sensitive, caffeine-induced Ca2+transients. These experiments suggest a new mechanism for cyclic nucleotide-mediated dilations through an increase in Ca2+spark frequency, caused by effects on SR Ca2+load and possibly on the RyR channel, which leads to increased STOC frequency, membrane potential hyperpolarization, closure of voltage-dependent Ca2+channels, decrease in arterial wall Ca2+, and, ultimately, vasodilation. |
| Databáze: | OpenAIRE |
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