Contribution of transient and sustained calcium influx, and sensitization to depolarization-induced contractions of the intact mouse aorta.
Contribution of transient and sustained calcium influx, and sensitization to depolarization-induced contractions of the intact mouse aorta.
复制标题
瞬时和持续钙涌入的贡献，以及对去极化诱导的完整小鼠主动脉收缩的敏感性。
DOI：
10.1186/1472-6793-12-9
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发表时间：
2012-09-03
期刊：
影响因子：
--
通讯作者：
Bult H
中科院分区：
文献类型：
--
作者：
Fransen P;Van Hove CE;van Langen J;Schrijvers DM;Martinet W;De Meyer GR;Bult H
离体血管平滑肌细胞L-型钙通道的电生理研究表明，这些细胞的去极化引起了短暂的和时间无关的钙电流。持续的，非失活电流发生在电压依赖性激活和失活重叠的电压（电压窗口），其对基础张力或主动张力在较大的多细胞血管制备目前尚不清楚。本研究探讨了窗口钙内流是否影响多细胞C57 B16小鼠主动脉节段的等长收缩。通过增加细胞外K+浓度，在固定膜电位的情况下，测量主动脉节段细胞内Ca 2+（Cai 2+，Fura-2）、膜电位和等长力。高于20 mM的K+诱发的双相收缩，这是不受抑制IP 3-或Ca 2+诱导的Ca 2+释放与2-氨基乙氧基二苯基硼酸盐或ryanodine，分别排除了细胞内Ca 2+释放的贡献。快收缩力分量随Ca ~（2+）的增加而增加，而慢收缩力分量随Ca ~（2+）的减少而减少。在细胞外Ca ~（2+）缺乏的情况下，基础张力和Ca ~（2+）下降，去极化不能引起Ca ~（2+）信号或收缩。随后重新引入外部Ca 2+只引起缓慢的收缩，这是现在匹配Cai 2+增加。Ca ~（2+）达到稳态后，由于Ca ~（2+）对收缩成分的增敏作用，等长收缩力继续增加。慢力反应表现出钟形电压依赖性，被左克罗卡林超极化抑制，并被L型钙通道激动剂（BAY K8644）增强。小鼠主动脉节段对去极化的等长反应包括快速、短暂的收缩，随后通过Ca ~（2+）通道瞬时Ca ~（2+）内流完全阻断。在去极化过程中没有完全恢复的Ca 2+通道启动了第二个持续的收缩相，这与持续的非失活窗口Ca 2+内流相匹配。与致敏作用一起，该窗口L-型Ca 2+内流是小鼠主动脉平滑肌的基础张力和主动张力的主要决定因素。
Electrophysiological studies of L-type Ca2+ channels in isolated vascular smooth muscle cells revealed that depolarization of these cells evoked a transient and a time-independent Ca2+ current. The sustained, non-inactivating current occurred at voltages where voltage-dependent activation and inactivation overlapped (voltage window) and its contribution to basal tone or active tension in larger multicellular blood vessel preparations is unknown at present. This study investigated whether window Ca2+ influx affects isometric contraction of multicellular C57Bl6 mouse aortic segments. Intracellular Ca2+ (Cai2+, Fura-2), membrane potential and isometric force were measured in aortic segments, which were clamped at fixed membrane potentials by increasing extracellular K+ concentrations. K+ above 20 mM evoked biphasic contractions, which were not affected by inhibition of IP3- or Ca2+ induced Ca2+ release with 2-aminoethoxydiphenyl borate or ryanodine, respectively, ruling out the contribution of intracellular Ca2+ release. The fast force component paralleled Cai2+ increase, but the slow contraction coincided with Cai2+ decrease. In the absence of extracellular Ca2+, basal tension and Cai2+ declined, and depolarization failed to evoke Cai2+ signals or contraction. Subsequent re-introduction of external Ca2+ elicited only slow contractions, which were now matched by Cai2+ increase. After Cai2+ attained steady-state, isometric force kept increasing due to Ca2+- sensitization of the contractile elements. The slow force responses displayed a bell-shaped voltage-dependence, were suppressed by hyperpolarization with levcromakalim, and enhanced by an agonist of L-type Ca2+ channels (BAY K8644). The isometric response of mouse aortic segments to depolarization consists of a fast, transient contraction paralleled by a transient Ca2+ influx via Ca2+ channels which completely inactivate. Ca2+ channels, which did not completely inactivate during the depolarization, initiated a second, sustained phase of contraction, which was matched by a sustained non-inactivating window Ca2+ influx. Together with sensitization, this window L-type Ca2+ influx is a major determinant of basal and active tension of mouse aortic smooth muscle.