Modulation of intracellular Ca2+ via L-type calcium channels in heart cells by the autoantibody directed against the second extracellular loop of the alpha1-adrenoceptors
| Autor: | Danielle Jacques, Michel Bui, Michael L.X Fu, Rami Sukarieh, Nesrine El-Bizri, Ghassan Bkaily |
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| Rok vydání: | 2003 |
| Předmět: |
Agonist
Patch-Clamp Techniques Potassium Channels Calcium Channels L-Type Nifedipine Physiology medicine.drug_class Chick Embryo Methoxamine Sodium Channels Calcium Channels T-Type Fetus Physiology (medical) Receptors Adrenergic alpha-1 medicine Extracellular Animals Humans L-type calcium channel Myocytes Cardiac Patch clamp Cells Cultured Autoantibodies Fluorescent Dyes Pharmacology Aniline Compounds Voltage-dependent calcium channel Chemistry Autoantibody General Medicine Calcium Channel Blockers Myocardial Contraction Cell biology Xanthenes Calcium Adrenergic alpha-1 Receptor Agonists Intracellular medicine.drug |
| Zdroj: | Canadian journal of physiology and pharmacology. 81(3) |
| ISSN: | 0008-4212 |
| Popis: | The effects of methoxamine, a selective α1-adrenergic receptor agonist, and the autoantibody directed against the second extracellular loop of α1-adrenoceptors were studied on intracellular free Ca2+ levels using confocal microscopy and ionic currents using the whole-cell patch clamp technique in single cells of 10-day-old embryonic chick and 20-week-old fetal human hearts. We observed that like methoxamine, the autoantibody directed against the second extracellular loop of α1-adrenoreceptors significantly increased the L-type calcium current (ICa(L)) but had no effect on the T-type calcium current (ICa(T)), the delayed outward potassium current, or the fast sodium current. This effect of the autoantibody was prevented by a prestimulation of the receptors with methoxamine and vice versa. Moreover, treating the cells with prazosin, a selective α1-adrenergic receptor antagonist blocked the methoxamine and the autoantibody-induced increase in ICa(L), respectively. In absence of prazosin, both methoxamine and the autoantibody showed a substantial enhancement in the frequency of cell contraction and that of the concomitant cytosolic and nuclear free Ca2+ variations. The subsequent addition of nifedipine, a specific L-type Ca2+ channel blocker, reversed not only the methoxamine or the autoantibody-induced effect but also completely abolished cell contraction. These results demonstrated that functional α1-adrenoceptors exist in both 10-day-old embryonic chick and 20-week-old human fetal hearts and that the autoantibody directed against the second extracellular loop of this type of receptors plays an important role in stimulating their activity via activation of L-type calcium channels. This loop seems to have a functional significance by being the target of α1-receptor agonists like methoxamine.Key words: α1-adrenoceptor, autoantibody, heart cells, calcium, ion channels, confocal microscopy. |
| Databáze: | OpenAIRE |
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