Modulation of intracellular Ca2+ levels by Scorpaenidae venoms

被引:16
作者
Church, JE [1 ]
Moldrich, RX [1 ]
Beart, PM [1 ]
Hodgson, WC [1 ]
机构
[1] Monash Univ, Dept Pharmacol, Monash Venom Grp, Clayton, Vic 3800, Australia
基金
英国医学研究理事会;
关键词
fish venoms; cultured neurones; chick biventer cervicis muscle; calcium; antivenom;
D O I
10.1016/S0041-0101(03)00038-2
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The crude venoms of the soldierfish (Gymnapistes marmoratus), the lionfish (Pterois volitans) and the stonefish (Synanceia trachynis) display pronounced neuromuscular activity. Since [Ca2+](i) is a key regulator in many aspects of neuromuscular function we sought to determine its involvement in the neuromuscular actions of the venoms. In the chick biventer cervicis muscle, all three venoms produced a sustained contraction (approx 20-30% of 1 mM acetylcholine). Blockade of nicotinic receptors with tubocurarine (10 muM) failed to attenuate the contractile response to either G. marmoratus venom or P. volitans venom, but produced slight inhibition of the response to S. trachynis venom. All three venoms produced a rise in intracellular Ca2+ (approx. 200-300% of basal) in cultured murine cortical neurons. The Ca2+-channel blockers omega-conotoxin MVIIC, omega-conotoxin GVIA, omega-agatoxin IVa and nifedipine (each at 1 muM) potentiated the increase in [Ca2+](i) in response to G. marmoratus venom and P. volitans venom, while attenuating the response to S. trachynis venom. Removal of extracellular Ca2+, replacement of Ca2+ with La3+ (0.5 mM), or addition of stonefish antivenom (3 units/ml) inhibited both the venom-induced increase in [Ca2+](i) in cultured neurones and contraction in chick biventer cervicis muscle. Venom-induced increases in [Ca2+](i) correlated with an increased cell death of cultured neurones as measured using propidium iodide (1 mug/ml). Morphological analysis revealed cellular swelling and neurite loss consistent with necrosis. These data indicate that the effects of all three venoms are due in part to an increase in intracellular Ca2+, possibly via the formation of pores in the cellular membrane which, under certain conditions, can lead to necrosis. (C) 2003 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:679 / 689
页数:11
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