Effects of external K+ on depletion-induced Ca2+ entry in rat ileal smooth muscle.
The effects of K+ on Ca2+ influx after transient depletion of Ca2+ stores with carbachol and long-lasting depletion with thapsigarin or ryanodine were examined in fura-2-loaded rat ileal smooth muscle. After transient depletion of Ca2+ stores, application of Ca2+ caused a rise in [Ca2+]i and a contraction, both of which were increased with increasing K+ applied simultaneously in the absence of methoxyverapamil, but were decreased in its presence. In tissues, long-lasting depletion of Ca2+ stores treated with thapsigarin or ryanodine, [Ca2+]i and tension were dose dependently increased by the application of Ca2+ regardless of the absence or presence of methoxyverapamil. These responses were inhibited by K+ replacement of Na+ in a dose-dependent manner and the inhibitory action of K+ was attenuated by increasing extracellular Ca2+. The influx of Mn2+ was much greater in the tissues pretreated with thapsigarin or ryanodine than in untreated tissues. The enhanced Mn2+ influx was inhibited by the replacement of Na+ with K+. These results provide further evidence for the presence of a Ca2+ entry mechanism evoked by the depletion of Ca2+ stores in rat ileal smooth muscle, and suggest that there are two types of Ca2+ entry pathways to refill Ca2+ stores, one sensitive and the other insensitive to Ca2+ channel blockers. Ca2+ entry through the latter pathway is inhibited by increasing external K+, perhaps due to a reduction of the electrochemical gradient for Ca2+ across the plasma membrane.
Laboratory of Pharmacology, School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
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Tabo
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Ohta
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Ito
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Nakazato
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002217:Carbachol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007082:Ileum / Q000187:drug effects* / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012433:Ryanodine / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology
D004791:Enzyme Inhibitors; D007211:Indoles; D018721:Muscarinic Agonists; D012433:Ryanodine; D019284:Thapsigargin; D002217:Carbachol; D000252:Calcium-Transporting ATPases; D011188:Potassium; D002118:Calcium; C000543:cyclopiazonic acid