Inhibition of CaT1 channel activity by a noncompetitive IP3 antagonist

被引:14
作者
Vassilev, PM
Peng, JB
Johnson, J
Hediger, MA
Brown, EM
机构
[1] Brigham & Womens Hosp, Dept Med, Div Endocrine Hypertens, Boston, MA 02115 USA
[2] Brigham & Womens Hosp, Dept Med, Div Renal, Boston, MA 02115 USA
[3] Brigham & Womens Hosp, Dept Med, Membrane Biol Program, Boston, MA 02115 USA
[4] Harvard Univ, Sch Med, Boston, MA 02115 USA
关键词
calcium; single channels; voltage-dependence; hyperpolarization-activated currents; IP3;
D O I
10.1006/bbrc.2000.4110
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A newly cloned, human epithelial Ca2+ transport protein (CaT1.) was expressed in Xenopus laevis oocytes, and its single channel characteristics were examined. The CaT1 channel shows a strong dependence upon hyperpolarizing voltages, being activated by very negative voltages. The probability of channel opening and mean open times increase substantially at more negative voltages in the range of -90 to -160 mV. In addition, CaT1 channel activity was markedly inhibited by micromolar levels of a noncompetitive antagonist of the IF, receptor originally isolated from a marine sponge, Xestospongin C. This inhibitory effect could be mediated indirectly via the binding of Xestospongin C to the inositol-trisphosphate (IP3) receptor or, alternatively, by a direct action on the CaT1 channel itself. Independent of its mechanism of action in inhibiting CaT1, Xestospongin C will provide a useful tool for elucidating the physiological role(s) of this novel epithelial Ca2+ channel. (C) 2001 Academic Press.
引用
收藏
页码:145 / 150
页数:6
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