Hayoz Sebastien, Pettis Jessica, Bradley Vanessa, Segal Steven S, Jackson William F
Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan.
College of Veterinary Medicine, Michigan State University, East Lansing, Michigan.
Am J Physiol Heart Circ Physiol. 2017 Jun 1;312(6):H1203-H1214. doi: 10.1152/ajpheart.00679.2016. Epub 2017 Apr 21.
Inward rectifier K channels (K) may contribute to skeletal muscle blood flow regulation and adapt to advanced age. Using mouse abdominal wall superior epigastric arteries (SEAs) from either young (3-6 mo) or old (24-26 mo) male C57BL/6 mice, we investigated whether SEA smooth muscle cells (SMCs) express functional K channels and how aging may affect K function. Freshly dissected SEAs were either enzymatically dissociated to isolate SMCs for electrophysiological recording (perforated patch) and mRNA expression or used intact for pressure myography. With 5 mM extracellular K concentration ([K]), exposure of SMCs to the K blocker Ba (100 μM) had no significant effect ( > 0.05) on whole cell currents elicited by membrane potentials spanning -120 to -30 mV. Raising [K] to 15 mM activated Ba-sensitive K currents between -120 and -30 mV, which were greater in SMCs from old mice than in SMCs from young mice ( < 0.05). Pressure myography of SEAs revealed that while aging decreased maximum vessel diameter by ~8% ( < 0.05), it had no significant effect on resting diameter, myogenic tone, dilation to 15 mM [K], Ba-induced constriction in 5 mM [K], or constriction induced by 15 mM [K] in the presence of Ba ( > 0.05). Quantitative RT-PCR revealed SMC expression of K2.1 and K2.2 mRNA that was not affected by age. Barium-induced constriction of SEAs from young and old mice suggests an integral role for K in regulating resting membrane potential and vasomotor tone. Increased functional expression of K channels during advanced age may compensate for other age-related changes in SEA function. Ion channels are integral to blood flow regulation. We found greater functional expression of inward rectifying K channels in smooth muscle cells of resistance arteries of mouse skeletal muscle with advanced age. This adaptation to aging may contribute to the maintenance of vasomotor tone and blood flow regulation during exercise.
内向整流钾通道(K)可能有助于骨骼肌血流调节并适应衰老。我们使用来自年轻(3 - 6个月)或老年(24 - 26个月)雄性C57BL/6小鼠的小鼠腹壁上腹壁动脉(SEA),研究了SEA平滑肌细胞(SMC)是否表达功能性K通道以及衰老如何影响K功能。将新鲜解剖的SEA进行酶解以分离SMC用于电生理记录(穿孔膜片钳)和mRNA表达,或完整用于压力肌电图检查。在细胞外钾浓度([K])为5 mM时,将SMC暴露于钾通道阻滞剂钡(100 μM)对跨膜电位在 -120至 -30 mV范围内引发的全细胞电流无显著影响(P>0.05)。将[K]提高到15 mM可激活 -120至 -30 mV之间对钡敏感的钾电流,老年小鼠SMC中的该电流大于年轻小鼠SMC中的电流(P<0.05)。SEA的压力肌电图显示,虽然衰老使最大血管直径减小约8%(P<0.05),但对静息直径、肌源性张力、对[K]为15 mM的舒张、在[K]为5 mM时钡诱导的收缩或在存在钡的情况下[K]为15 mM诱导的收缩均无显著影响(P>0.05)。定量逆转录聚合酶链反应显示K2.1和K2.2 mRNA在SMC中的表达不受年龄影响。钡诱导的年轻和老年小鼠SEA收缩表明K在调节静息膜电位和血管舒缩张力中起重要作用。衰老过程中钾通道功能表达增加可能补偿SEA功能中其他与年龄相关的变化。离子通道对血流调节至关重要。我们发现老年小鼠骨骼肌阻力动脉平滑肌细胞中内向整流钾通道的功能表达更高。这种对衰老的适应性可能有助于运动期间维持血管舒缩张力和血流调节。