Experimental Anaesthesiology, Department of Anaesthesiology and Intensive Care Medicine, Medical University of Graz, Auenbruggerplatz 5, 8036 Graz, Austria.
Department of Internal Medicine, Division of Pulmonology, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria.
Biomolecules. 2021 Nov 3;11(11):1629. doi: 10.3390/biom11111629.
Potassium ion concentrations, controlled by ion pumps and potassium channels, predominantly govern a cell's membrane potential and the tone in the vessels. Calcium-activated potassium channels respond to two different stimuli-changes in voltage and/or changes in intracellular free calcium. Large conductance calcium-activated potassium (BKCa) channels assemble from pore forming and various modulatory and auxiliary subunits. They are of vital significance due to their very high unitary conductance and hence their ability to rapidly cause extreme changes in the membrane potential. The pathophysiology of lung diseases in general and pulmonary hypertension, in particular, show the implication of either decreased expression and partial inactivation of BKCa channel and its subunits or mutations in the genes encoding different subunits of the channel. Signaling molecules, circulating humoral molecules, vasorelaxant agents, etc., have an influence on the open probability of the channel in pulmonary arterial vascular cells. BKCa channel is a possible therapeutic target, aimed to cause vasodilation in constricted or chronically stiffened vessels, as shown in various animal models. This review is a comprehensive collation of studies on BKCa channels in the pulmonary circulation under hypoxia (hypoxic pulmonary vasoconstriction; HPV), lung pathology, and fetal to neonatal transition, emphasising pharmacological interventions as viable therapeutic options.
钾离子浓度受离子泵和钾通道的控制，主要调节细胞的膜电位和血管张力。钙激活钾通道对两种不同的刺激做出反应——电压变化和/或细胞内游离钙的变化。大电导钙激活钾（BKCa）通道由形成孔道的亚基和各种调节亚基及辅助亚基组成。由于其具有非常高的单通道电导，因此能够迅速引起膜电位的剧烈变化，因此具有重要的生理意义。一般来说，肺部疾病的病理生理学，尤其是肺动脉高压，表明 BKCa 通道及其亚基的表达减少和部分失活，或者编码通道不同亚基的基因发生突变。信号分子、循环体液分子、血管舒张剂等，影响肺动脉血管细胞中通道的开放概率。BKCa 通道是一种可能的治疗靶点，旨在引起收缩或慢性僵硬血管的血管舒张，这在各种动物模型中得到了证实。本综述全面整理了低氧（低氧性肺血管收缩；HPV）、肺部病理学和胎儿到新生儿过渡期间肺循环中 BKCa 通道的研究，强调了药理学干预作为可行的治疗选择。
