PT  - JOURNAL ARTICLE
AU  - Kazuo Ishii
AU  - Kaoru M. Ito
AU  - Daisuke Uemura
AU  - Katsuaki Ito
TI  - Possible Mechanism of Palytoxin-Induced Ca<sup>++</sup>Mobilization in Porcine Coronary Artery
DP  - 1997 Jun 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1077--1084
VI  - 281
IP  - 3
4099  - http://jpet.aspetjournals.org/content/281/3/1077.short
4100  - http://jpet.aspetjournals.org/content/281/3/1077.full
SO  - J Pharmacol Exp Ther1997 Jun 01; 281
AB  - 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 μM verapamil or 1 μM 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++]iin 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. The American Society for Pharmacology and Experimental Therapeutics