Bicarbonate is one of the major anions in mammalian tissues and extracellular fluids. Along with accompanying H+, HCO3- is generated from CO2 and H2 O, either spontaneously or via the catalytic activity of carbonic an...Bicarbonate is one of the major anions in mammalian tissues and extracellular fluids. Along with accompanying H+, HCO3- is generated from CO2 and H2 O, either spontaneously or via the catalytic activity of carbonic anhydrase. It serves as a component of the major buffer system, thereby playing a critical role in pH homeostasis. Bicarbonate can also be utilized by a variety of ion transporters, often working in coupled systems, to transport other ions and organic substrates across cell membranes. The functions of HCO3- and HCO3--transporters in epithelial tissues have been studied extensively, but their functions in heart are less well understood. Here we review studies of the identities and physiological functions of Cl-/HCO3- exchangers and Na+/HCO3-cotransporters of the SLC4 A and SLC26 A families in heart. We also present RNA Seq analysis of their cardiac mRNA expression levels. These studies indicate that slc4a3(AE3) is the major Cl-/HCO3- exchanger and plays a protective role in heart failure, and that Slc4a4(NBCe1) is the major Na+/HCO3- cotransporter and affects action potential duration. In addition, previous studies show that HCO3- has a positive inotropic effect in the perfused heart that is largely independent of effects on intracellular Ca2+. The importance of HCO3- in the regulation of contractility is supported by experiments showing that isolated cardiomyocytes exhibit sharply enhanced contractility, with no change in Ca2+ transients, when switched from Hepes-buffered to HCO3-- buffered solutions. These studies demonstrate that HCO3- and HCO3--handling proteins play important roles in the regulation of cardiac function.展开更多
采用扫描电镜观察了不同碱度(0、2、4 g/L Na HCO_3)胁迫对尼罗罗非鱼(Oreochromis niloticus)鳃离子细胞形态变化的影响,并采用免疫组化技术观察了鳃、肾、肠中4个HCO_3^-转运因子碳酸酐酶(CAⅡ、CAⅣ)、碳酸氢钠协同转运载体(SLC4A4)...采用扫描电镜观察了不同碱度(0、2、4 g/L Na HCO_3)胁迫对尼罗罗非鱼(Oreochromis niloticus)鳃离子细胞形态变化的影响,并采用免疫组化技术观察了鳃、肾、肠中4个HCO_3^-转运因子碳酸酐酶(CAⅡ、CAⅣ)、碳酸氢钠协同转运载体(SLC4A4)、Cl^-/HCO_3^-离子交换体(SLC26A6)的阳性反应变化。扫描电镜结果表明,鳃离子细胞分布在鳃小片基部。根据其表面开孔形状和尺寸,可分为Ⅰ型、Ⅱ型、Ⅲ型和Ⅳ型4种亚型,各亚型离子细胞的开孔尺寸随碱度胁迫强度增高呈正比增大,Ⅲ型离子细胞开孔尺寸变化最明显(P<0.01);离子细胞总数目也随碱度升高而增加,Ⅲ型离子细胞数目上升最为显著(P<0.01)。免疫组化结果表明,在淡水、碱水组中,CAⅡ、CAⅣ、SLC4A4、SLC26A6在鳃小片基部和肾中均有阳性反应,且随着碱度升高,阳性反应增强,但在肠道中未观察到阳性反应。本研究结果初步表明,尼罗罗非鱼可通过鳃离子细胞形态和数量调节适应碱度变化,鳃和肾为主要应答调节器官。展开更多
基金Supported by National Institutes of Health Grants HL061974 to Shull GEand ES017263 to Wang HS
文摘Bicarbonate is one of the major anions in mammalian tissues and extracellular fluids. Along with accompanying H+, HCO3- is generated from CO2 and H2 O, either spontaneously or via the catalytic activity of carbonic anhydrase. It serves as a component of the major buffer system, thereby playing a critical role in pH homeostasis. Bicarbonate can also be utilized by a variety of ion transporters, often working in coupled systems, to transport other ions and organic substrates across cell membranes. The functions of HCO3- and HCO3--transporters in epithelial tissues have been studied extensively, but their functions in heart are less well understood. Here we review studies of the identities and physiological functions of Cl-/HCO3- exchangers and Na+/HCO3-cotransporters of the SLC4 A and SLC26 A families in heart. We also present RNA Seq analysis of their cardiac mRNA expression levels. These studies indicate that slc4a3(AE3) is the major Cl-/HCO3- exchanger and plays a protective role in heart failure, and that Slc4a4(NBCe1) is the major Na+/HCO3- cotransporter and affects action potential duration. In addition, previous studies show that HCO3- has a positive inotropic effect in the perfused heart that is largely independent of effects on intracellular Ca2+. The importance of HCO3- in the regulation of contractility is supported by experiments showing that isolated cardiomyocytes exhibit sharply enhanced contractility, with no change in Ca2+ transients, when switched from Hepes-buffered to HCO3-- buffered solutions. These studies demonstrate that HCO3- and HCO3--handling proteins play important roles in the regulation of cardiac function.
文摘采用扫描电镜观察了不同碱度(0、2、4 g/L Na HCO_3)胁迫对尼罗罗非鱼(Oreochromis niloticus)鳃离子细胞形态变化的影响,并采用免疫组化技术观察了鳃、肾、肠中4个HCO_3^-转运因子碳酸酐酶(CAⅡ、CAⅣ)、碳酸氢钠协同转运载体(SLC4A4)、Cl^-/HCO_3^-离子交换体(SLC26A6)的阳性反应变化。扫描电镜结果表明,鳃离子细胞分布在鳃小片基部。根据其表面开孔形状和尺寸,可分为Ⅰ型、Ⅱ型、Ⅲ型和Ⅳ型4种亚型,各亚型离子细胞的开孔尺寸随碱度胁迫强度增高呈正比增大,Ⅲ型离子细胞开孔尺寸变化最明显(P<0.01);离子细胞总数目也随碱度升高而增加,Ⅲ型离子细胞数目上升最为显著(P<0.01)。免疫组化结果表明,在淡水、碱水组中,CAⅡ、CAⅣ、SLC4A4、SLC26A6在鳃小片基部和肾中均有阳性反应,且随着碱度升高,阳性反应增强,但在肠道中未观察到阳性反应。本研究结果初步表明,尼罗罗非鱼可通过鳃离子细胞形态和数量调节适应碱度变化,鳃和肾为主要应答调节器官。
