Greenberg R M
Marine Biological Laboratory, 7 MBL Street, Woods Hole, MA 02543, USA.
Parasitology. 2005;131 Suppl:S97-108. doi: 10.1017/S0031182005008346.
Transient changes in calcium (Ca2+) levels regulate a wide variety of cellular processes, and cells employ both intracellular and extracellular sources of Ca2+ for signalling. Praziquantel, the drug of choice against schistosomiasis, disrupts Ca2+ homeostasis in adult worms. This review will focus on voltage-gated Ca2+ channels, which regulate levels of intracellular Ca2+ by coupling membrane depolarization to entry of extracellular Ca2+. Ca2+ channels are members of the ion channel superfamily and represent essential components of neurons, muscles and other excitable cells. Ca2+ channels are membrane protein complexes in which the pore-forming alpha1 subunit is modulated by auxiliary subunits such as beta and alpha2delta. Schistosomes express two Ca2+ channel beta subunit subtypes: a conventional subtype similar to beta subunits found in other vertebrates and invertebrates and a novel variant subtype with unusual structural and functional properties. The variant schistosome beta subunit confers praziquantel sensitivity to an otherwise praziquantel-insensitive mammalian Ca2+ channel, implicating it as a mediator of praziquantel action.
钙（Ca2+）水平的瞬时变化调节着多种细胞过程，细胞利用细胞内和细胞外的Ca2+来源进行信号传导。吡喹酮是治疗血吸虫病的首选药物，它会破坏成虫体内的Ca2+稳态。本综述将聚焦于电压门控Ca2+通道，该通道通过将膜去极化与细胞外Ca2+的内流相偶联来调节细胞内Ca2+水平。Ca2+通道是离子通道超家族的成员，是神经元、肌肉和其他可兴奋细胞的重要组成部分。Ca2+通道是膜蛋白复合物，其中形成孔道的α1亚基受β和α2δ等辅助亚基的调节。血吸虫表达两种Ca2+通道β亚基亚型：一种与其他脊椎动物和无脊椎动物中发现的β亚基类似的传统亚型，以及一种具有不寻常结构和功能特性的新型变体亚型。这种变体血吸虫β亚基赋予原本对吡喹酮不敏感的哺乳动物Ca2+通道对吡喹酮的敏感性，表明它是吡喹酮作用的介质。
