钙及钙通道阻滞剂对钠泵的影响。

The effects of calcium and calcium channel blockers on sodium pump.

作者信息

Stankovicová T, Zemková H, Breier A, Amler E, Burkhard M, Vyskocil F

机构信息

Faculty of Pharmacy, Department of Pharmacology and Toxicology, Bratislava, Slovak Republic.

出版信息

Pflugers Arch. 1995 Mar;429(5):716-21. doi: 10.1007/BF00373994.

DOI:10.1007/BF00373994

PMID:7792147

Abstract

The effects of 10 mM Ca2+ and Ca2+ channel blockers verapamil, diltiazem and flunarizine on the ouabain-sensitive electrogenic Na+, K+ pump activity of mouse diaphragm muscle fibres enriched with Na+ were compared with the changes in cytosolic [Ca2+]. The electrogenic Na+ pump activity produced by adding K+ to muscles previously bathed for 4 h in a K(+)-free, 2-mM [Ca2+] solution increased the resting membrane potential by about 18 mV. This hyperpolarization was completely inhibited after 10 min incubation in 10 mM Ca2+. Verapamil 10(-5) M, 10(-5) M diltiazem and 10(-7) M flunarizine effectively prevented the effect of elevated [Ca2+]. At these concentrations, these drugs did not affect the K(+)-induced hyperpolarization. In mouse diaphragm, the basal cytosolic [Ca2+] measured by the fluorescent indicator 1-[2-(5-carboxyoxazol-2-yl)-6- aminobenzofuran-5-oxy]2-(2'-amino-5'-methylphenoxy)ethane-N,N,N',N '- tetraacetic acid acetoxymethyl ester (fura-2/AM) was 261 +/- 6 nM. After 4 h in a Liley K(+)-free, 2 mM [Ca2+] solution, the cytosolic [Ca2+] increased to 314 +/- 28 nM. Increase in [Ca2+] from 2 to 10 mM caused a twofold increase of cytosolic [Ca2+] to 637 +/- 26 nM. This rise was, like the Ca(2+)-induced inhibition of electrogenic pump, prevented by 10(-5) M verapamil, 10(-5) M diltiazem and 10(-7) M flunarizine. The results suggest that substances which block Ca2+ entry into the cell prevent the Ca(2+)-induced inhibition of the Na+ pump.

摘要

将富含Na⁺的小鼠膈肌纤维中哇巴因敏感的生电Na⁺、K⁺泵活性上10 mM Ca²⁺及Ca²⁺通道阻滞剂维拉帕米、地尔硫䓬和氟桂利嗪的作用与胞质[Ca²⁺]的变化进行了比较。向先前在无K⁺、2 mM [Ca²⁺]溶液中孵育4小时的肌肉中添加K⁺所产生的生电Na⁺泵活性使静息膜电位增加了约18 mV。在10 mM Ca²⁺中孵育10分钟后，这种超极化被完全抑制。10⁻⁵ M维拉帕米、10⁻⁵ M地尔硫䓬和10⁻⁷ M氟桂利嗪有效地阻止了[Ca²⁺]升高的影响。在这些浓度下，这些药物不影响K⁺诱导的超极化。在小鼠膈肌中，用荧光指示剂1-[2-(5-羧基恶唑-2-基)-6-氨基苯并呋喃-5-氧基]2-(2'-氨基-5'-甲基苯氧基)乙烷-N,N,N',N'-四乙酸乙酰甲酯（fura-2/AM）测得的基础胞质[Ca²⁺]为261±6 nM。在Liley无K⁺、2 mM [Ca²⁺]溶液中孵育4小时后，胞质[Ca²⁺]增加到314±28 nM。[Ca²⁺]从2 mM增加到10 mM导致胞质[Ca²⁺]增加两倍，达到637±26 nM。这种升高，与Ca²⁺诱导的生电泵抑制一样，被10⁻⁵ M维拉帕米、10⁻⁵ M地尔硫䓬和10⁻⁷ M氟桂利嗪阻止。结果表明，阻止Ca²⁺进入细胞的物质可防止Ca²⁺诱导的Na⁺泵抑制。