INHIBITION OF N-TYPE AND L-TYPE CA2+ CHANNELS BY THE SPIDER VENOM TOXIN OMEGA-AGA-IIIA

被引:104
作者
MINTZ, IM [1 ]
VENEMA, VJ [1 ]
ADAMS, ME [1 ]
BEAN, BP [1 ]
机构
[1] UNIV CALIF RIVERSIDE, DEPT ENTOMOL, RIVERSIDE, CA 92521 USA
关键词
AGELENOPSIS-APERTA; NEUROTOXIN; CARDIAC MUSCLE; SENSORY NEURONS; HIPPOCAMPUS;
D O I
10.1073/pnas.88.15.6628
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Omega-Aga-IIIA, an 8.5-kDa peptide toxin isolated from the venom of Agelenopsis aperta, was found to be a highly potent inhibitor of Ca channels in cardiac muscle and in peripheral and central neurons of rats and frogs. Cardiac L-type Ca channels were completely (K(d) almost-equal-to 0.6 nM) blocked by omega-Aga-IIIA. In sensory neurons, the toxin inhibited most high-threshold Ca current but not T-type Ca current. Omega-Aga-IIIA blocked with similar potency (K(d) almost-equal-to 1.5 nM) both omega-conotoxin GVIA-sensitive and dihydropyridine-sensitive current components but left a fraction (almost-equal-to 35%) of high-threshold current that was also resistant to omega-conotoxin and dihydropyridines. The toxin blocks N- and L-type channels with equal potency and therefore may identify a high-affinity binding site common to these two Ca channel types.
引用
收藏
页码:6628 / 6631
页数:4
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