首页> 外文期刊>American Journal of Physiology >KCa channel insensitivity to Ca2+ sparks underlies fractional uncoupling in newborn cerebral artery smooth muscle cells.
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KCa channel insensitivity to Ca2+ sparks underlies fractional uncoupling in newborn cerebral artery smooth muscle cells.

机译:KCa通道对Ca2 +火花的不敏感性是新生脑动脉平滑肌细胞中部分解偶联的基础。

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In smooth muscle cells, localized intracellular Ca2+ transients, termed "Ca2+ sparks," activate several large-conductance Ca2+-activated K+ (KCa) channels, resulting in a transient KCa current. In some smooth muscle cell types, a significant proportion of Ca2+ sparks do not activate KCa channels. The goal of this study was to explore mechanisms that underlie fractional Ca2+ spark-KCa channel coupling. We investigated whether membrane depolarization or ryanodine-sensitive Ca2+ release (RyR) channel activation modulates coupling in newborn (1- to 3-day-old) porcine cerebral artery myocytes. At steady membrane potentials of -40, 0, and +40 mV, mean transient KCa current frequency was approximately 0.18, 0.43, and 0.26 Hz and KCa channel activity [number of KCa channels activated by Ca2+ sparksxopen probability of KCa channels at peak of Ca2+ sparks (NPo)] at the transient KCa current peak was approximately 4, 12, and 24, respectively. Depolarization between -40 and +40 mV increased KCa channel sensitivityto Ca2+ sparks and elevated the percentage of Ca2+ sparks that activated a transient KCa current from 59 to 86%. In a Ca2+-free bath solution or in diltiazem, a voltage-dependent Ca2+ channel blocker, steady membrane depolarization between -40 and +40 mV increased transient KCa current frequency up to approximately 1.6-fold. In contrast, caffeine (10 microM), an RyR channel activator, increased mean transient KCa current frequency but did not alter Ca2+ spark-KCa channel coupling. These data indicate that coupling is increased by mechanisms that elevate KCa channel sensitivity to Ca2+ sparks, but not by RyR channel activation. Overall, KCa channel insensitivity to Ca2+ sparks is a prominent factor underlying fractional Ca2+ spark uncoupling in newborn cerebral artery myocytes.
机译:在平滑肌细胞中,称为“ Ca2 +火花”的局部细胞内Ca2 +瞬变激活了几个大电导的Ca2 +激活的K +(KCa)通道,从而产生了瞬态KCa电流。在某些平滑肌细胞类型中,很大比例的Ca2 +火花不会激活KCa通道。这项研究的目的是探索部分Ca2 +火花-KCa通道耦合基础的机制。我们调查了膜去极化或ryanodine敏感的Ca 2+释放(RyR)通道激活是否调节新生(1-3天大)猪脑动脉心肌细胞的偶联。在-40、0和+40 mV的稳定膜电位下,平均瞬时KCa电流频率约为0.18、0.43和0.26 Hz,并且KCa通道活动性[Ca2 +激活的KCa通道数会激发出在Ca2 +峰值处KCa通道的开放概率瞬时KCa电流峰值处的电火花(NPo)分别约为4、12和24。 -40至+40 mV之间的去极化会增加KCa通道对Ca2 +火花的敏感性,并将激活瞬态KCa电流的Ca2 +火花百分比从59%提高到86%。在不含Ca2 +的浴液或地尔硫卓中,电压依赖性Ca2 +通道阻滞剂在-40至+40 mV之间稳定地进行膜去极化,可将瞬态KCa电流频率提高至大约1.6倍。相比之下,RyR通道激活剂咖啡因(10 microM)增加了平均瞬态KCa电流频率,但并未改变Ca2 + spark-KCa通道耦合。这些数据表明,通过提高KCa通道对Ca2 +火花的敏感性的机制可以增强耦合,但不能通过RyR通道激活来增强耦合。总体而言,KCa通道对Ca2 +火花的不敏感性是新生脑动脉肌细胞中部分Ca2 +火花解偶联的重要因素。

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