Abstract
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.
Footnotes
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Send reprint requests to: Dr. Katsuaki Ito, Department of Veterinary Pharmacology, Faculty of Agriculture, Miyazaki University, Miyazaki 889-21, Japan.
- Abbreviations:
- PTX
- palytoxin
- [Ca++]
- cytosolic Ca++ concentration
- [Na+]
- cytosolic Na+ concentration
- PSS
- physiological saline solution
- R340/380
- the ratio of fluorescence at emission of 500 nm after excitation at wavelength of 340 nm to that after excitation of 380 nm
- NMDG
- N-methyl-d-glucamine
- EGTA
- ethyleneglycol bis(β-aminoehtyl ether)-N,N′-tetraacetic acid
- SR
- sarcoplasmic reticulum
- Received November 11, 1996.
- Accepted February 24, 1997.
- The American Society for Pharmacology and Experimental Therapeutics
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