期刊
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
卷 294, 期 1, 页码 H272-H284出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.00216.2007
关键词
membrane potential; intracellular calcium; patch clamp; potassium currents; 4-aminopyridine
资金
- NHLBI NIH HHS [HL 44455, HL 73895, HL 67250] Funding Source: Medline
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL067250, R01HL044455, R01HL073895] Funding Source: NIH RePORTER
Increased pressure-induced ( myogenic) tone in small uteroplacental arteries from late pregnant ( LP) rats has been previously observed. In this study, we hypothesized that this response may result from a diminished activity of vascular smooth muscle cell (SMC) voltage-gated delayed-rectifier K+ (Kv) channels, leading to membrane depolarization, augmented Ca2+ influx, and vasoconstriction ( tone). Elevation of intraluminal pressure from 10 to 60 and 100 mmHg resulted in a marked, diltiazem-sensitive rise in SMC cytosolic Ca2+ concentration ([Ca2+](i)) associated with a vasoconstriction of uteroplacental arteries of LP rats. In contrast, these changes were significantly diminished in uterine arteries from nonpregnant (NP) rats. Gestational augmentation of pressure-induced Ca2+ influx through L-type Ca2+ channels was associated with an enhanced SMC depolarization, the appearance of electrical and [Ca2+](i) oscillatory activities, and vasomotion. Exposure of vessels from NP animals to 4-aminopyridine, which inhibits the activity of Kv channels, mimicked the effects of pregnancy by increasing pressure-induced depolarization, elevation of [Ca2+](i), and development of myogenic tone. Furthermore, currents through Kv channels were significantly reduced in myocytes dissociated from arteries of LP rats compared with those of NP controls. Based on these results, we conclude that decreased Kv channel activity contributes importantly to enhanced pressure-induced depolarization, Ca2+ entry, and increase in myogenic tone present in uteroplacental arteries from LP rats.
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