Possible mechanism of palytoxin-induced Ca++ mobilization in porcine coronary artery.
We investigated the mechanisms involved in palytoxin (PTX)-induced cytosolic Ca++ ([Ca++]i) mobilization and contraction in porcine coronary arteries using a fluorescent Ca++ indicator fura-PE3. PTX (1 pM-10 nM) induced concentration-dependent and sustained increases in [Ca++]i and tension, both of which were partially inhibited by 10 microM verapamil or 1 microM nicardipine. In Ca++-free solution containing 1 mM EGTA, PTX did not increase [Ca++]i. In nominally Ca++-free solution (no EGTA), however, PTX increased [Ca++]i, which was presumed to be due to release of Ca++ from intracellular stores. PTX-induced rise in [Ca++]i was dependent on external Na+ because it did not increase [Ca++]i in Na+-free solutions containing verapamil. An increase in [Ca++]i in response to 65.4 mM KCl also involved a verapamil-resistant but external Na+-dependent component. After blockage of voltage-dependent Ca++ channels with verapamil, elevation of external K+ to 65.4 mM enhanced the responses of [Ca++]i and tension to PTX. PTX at 10 and 100 pM depolarized the membrane by 4.5 +/- 0.8 and 18.6 +/- 1.7 mV, respectively. Because PTX is known to increase membrane Na+ permeability, our results suggest that an increase in cytosolic Na+ and the depolarization were primary events required for the PTX-induced Ca++ mobilization and that Ca++ influxes through voltage-dependent Ca++ channels and Na+-Ca++ exchange and Ca++ release from Ca++ stores, which was triggered by increased Ca++ entry, were responsible for the PTX-induced increase in [Ca++]i.
Ishii
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Department of Veterinary Pharmacology, Faculty of Agriculture, Miyazaki University, Japan.
Ito
K M
KM
Uemura
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Ito
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D000178:Acrylamides / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003064:Cnidarian Venoms; D003331:Coronary Vessels / Q000187:drug effects*; D013552:Swine; D000095702:Polyether Toxins
D000178:Acrylamides; D002118:Calcium; D003064:Cnidarian Venoms; C010272:palytoxin; D000095702:Polyether Toxins