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Capacitative Ca2+ entry associated with alpha1-adrenoceptors in rat aorta
M A Noguera1, M D Ivorra, S Chuliá
1Departamento de Farmacologia, Facultad de Farmacia, Universitat de Valencia, Spain.
Naunyn-Schmiedeberg'S Archives of Pharmacology
|July 1, 1997
Summary
Noradrenaline depletes internal calcium stores in rat aorta, triggering extracellular calcium entry. This entry, mediated by specific ion channels, influences both store refilling and smooth muscle contraction.
Area of Science:
- Pharmacology
- Cardiovascular Physiology
- Cellular Biology
Background:
- Noradrenaline induces biphasic contractions in rat aorta via distinct intracellular calcium (Ca2+) pools.
- Depletion of these stores signals extracellular Ca2+ entry, crucial for refilling and maintaining tone.
Purpose of the Study:
- To investigate the ionic channels involved in the increase in resting tone (IRT) following noradrenaline-induced Ca2+ store depletion.
- To elucidate the role of specific ion channels in the refilling of intracellular Ca2+ compartments.
Main Methods:
- Experiments conducted on rat aorta.
- Utilized noradrenaline to deplete internal Ca2+ stores.
- Investigated the effects of nimodipine and cromakalim, alone and in combination with glibenclamide, on Ca2+ handling and contractility.
Main Results:
- Nimodipine selectively inhibited IRT, suggesting involvement of dihydropyridine-sensitive Ca2+ channels.
- Glibenclamide attenuated nimodipine's effect, indicating interaction with ATP-dependent K+ channels.
- Cromakalim also inhibited IRT, with its action antagonized by glibenclamide, further implicating ATP-dependent K+ channels.
- Nimodipine inhibited refilling of the tonic Ca2+ compartment, while cromakalim affected refilling of both phasic and tonic compartments.
Conclusions:
- Rat aorta contraction involves distinct phasic and tonic responses mediated by separate Ca2+ pools.
- The phasic response involves a Ca2+ compartment refilled via a cromakalim-sensitive, dihydropyridine-insensitive channel.
- The tonic response involves a Ca2+ compartment refilled via a channel sensitive to both cromakalim and dihydropyridine, which also mediates IRT and is modulated by ATP-dependent K+ channels.