Protective effect of l-cis-diltiazem on hypercontracture of rat myocytes induced by veratridine

The protective effect of l- cis-diltiazem, the stereoisomer of d- cis-diltiazem, was studied against the veratridine-induced hypercontracture of rat myocytes. Veratridine increased both [Na +] i and [Ca 2+] i, but did not cause hypercontracture in the absence of extracellular Ca 2+. Both l- cis-dilt...

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Bibliographic Details
Published in:European journal of pharmacology 1996-12, Vol.317 (2), p.401-406
Main Authors: Itogawa, Emiko, Kurosawa, Hideo, Yabana, Hideo, Murata, Sakae
Format: Article
Language:English
Subjects:
Animals
Benzofurans
Biological and medical sciences
Ca 2+ overload
Calcium - metabolism
Calcium Channel Blockers - pharmacology
Cardiovascular system
d- cis-Diltiazem
Diltiazem - pharmacology
Fluorescent Dyes
Fura-2
Heart - drug effects
In Vitro Techniques
l- cis-Diltiazem
Male
Medical sciences
Miscellaneous
Myocardial Contraction - drug effects
Myocardium - cytology
Myocardium - metabolism
Myocyte
Na + overload
Papillary Muscles - drug effects
Pharmacology. Drug treatments
Phthalic Acids
Rat
Rats
Rats, Sprague-Dawley
Sodium - metabolism
Stereoisomerism
Veratridine
Veratridine - pharmacology
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Summary:The protective effect of l- cis-diltiazem, the stereoisomer of d- cis-diltiazem, was studied against the veratridine-induced hypercontracture of rat myocytes. Veratridine increased both [Na +] i and [Ca 2+] i, but did not cause hypercontracture in the absence of extracellular Ca 2+. Both l- cis-diltiazem (0.1–10 μM) and d- cis-diltiazem (10–30 μM) inhibited the hypercontracture and the increase in [Ca 2+] i in a concentration-dependent manner. However, l- cis-diltiazem did not exert a negative inotropic effect in K + (20 mM)-depolarized rat papillary muscles even at a dose of 10 μM. As seen in the case of tetrodotoxin, l- cis-diltiazem and d- cis-diltiazem also suppressed the increase in [Na +] i. The results show that l- cis-diltiazem prevents the veratridine-induced hypercontracture of myocytes by suppression of the [Ca 2+] i increase. The attenuation of the [Ca 2+] i increase by l- cis-diltiazem was not dependent on inhibition of Ca 2+ channels, but was partly due to inhibition of excessive Na + entry via veratridine-modified Na + channels.
ISSN:0014-2999
1879-0712
DOI:10.1016/S0014-2999(96)00758-3