Abstract
Adequate blood flow through placental chorionic plate resistance arteries (CPAs) is necessary for oxygen and nutrient transfer to the fetus and a successful pregnancy. In non-placental vascular smooth muscle cells (SMCs), K+ channels regulate contraction, vascular tone and blood flow. Previous studies showed that K+ channel modulators alter CPA tone, but did not distinguish between effects on K+ channels in endothelial cells and SMCs. In this study, we developed a preparation of freshly isolated CPASMCs of normal pregnancy and investigated K+ channel expression and function. CPASMCs were isolated from normal human term placentas using enzymatic digestion. Purity and phenotype was confirmed with immunocytochemistry. Whole-cell patch clamp was used to assess K+ channel currents, and mRNA and protein expression was determined in intact CPAs and isolated SMCs with RT-PCR and immunostaining. Isolated SMCs expressed α-actin but not CD31, a marker of endothelial cells. CPASMCs and intact CPAs expressed h-caldesmon and non-muscle myosin heavy chain-2; phenotypic markers of contractile and synthetic SMCs respectively. Whole-cell currents were inhibited by 4-AP, TEA, charybdotoxin and iberiotoxin implicating functional Kv and BKCa channels. 1-EBIO enhanced whole cell currents which were abolished by TRAM-34 and reduced by apamin indicating activation of IKCa and SKCa respectively. BKCa, IKCa and SKCa3 mRNA and/or protein were expressed in CPASMCs and intact CPAs. This study provides the first direct evidence for functional Kv, BKCa, IKCa and SKCa channels in CPASMCs. These cells display a mixed phenotype implicating a dual role for CPASMCs in controlling both fetoplacental vascular resistance and vasculogenesis.
Highlights
Appropriate control of human placental blood flow is necessary for maximal exchange of oxygen and nutrients to the growing fetus and a successful pregnancy
chorionic plate arteries (CPAs) smooth muscle cell (CPASMC) excitation-contraction coupling is poorly understood and studies are currently hindered by the lack of a suitable single cell model of isolated CPASMCs
We developed a preparation of freshly isolated smooth muscle cells (SMCs) from CPAs of normal pregnancy and characterised K+ channel currents, mRNA and protein expression using whole-cell electrophysiology, immunocytochemistry and RT-PCR
Summary
Appropriate control of human placental blood flow is necessary for maximal exchange of oxygen and nutrients to the growing fetus and a successful pregnancy. Placental chorionic plate arteries (CPAs) branch from the umbilical arteries and are likely the primary determinants of fetoplacental vascular resistance as they have similar size characteristics (,500 mm) to systemic resistance vessels [1]. Fetoplacental blood vessels lack innervation and respond poorly to potent vasoactive agents of the systemic circulation [1,2]. A high flow/low resistance circulation is essential to promote sufficient maternal-fetal exchange of oxygen and nutrients. Appropriate regulation of SMC function, and fetoplacental vascular tone and blood flow, is necessary to facilitate maximal exchange of these substances and thereby support fetal growth. CPA smooth muscle cell (CPASMC) excitation-contraction coupling is poorly understood and studies are currently hindered by the lack of a suitable single cell model of isolated CPASMCs
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