ISSN:1420-4096    

DOI:10.1159/000174058

出版商:S. Karger AG    

年代:1996

数据来源: Karger

ISSN:1420-4096    

DOI:10.1159/000174059

出版商:S. Karger AG    

年代:1996

数据来源: Karger

ISSN:1420-4096    

DOI:10.1159/000174060

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

The atomic force microscope (AFM) was invented in 1986. It created the possibility to study the surfaces of biological material at the molecular level. The AFM is not only a microscope with atomic resolution (at least when applied to suitable samples) but is also an instrument with a broad variety of other applications. We present five examples demonstating the application of the AFM technique in different ways, mainly in renal epithelium. First, it was used as a high-resolution near-field microscope which generated images of canine kidney chromosomes. Second, dynamic changes of the plasma membrane of canine kidney cells were visualized with a resolution at least 10-fold greater than that obtainable by light microscopy. Third, the AFM was used as a tool which interacted directly with the plasma membrane of canine kidney cells. Fourth, due to its excellent resolution in the third dimension (namely height), continuous measurements of changes in ‘height’ of multimers of cloned plasma membrane potassium channel proteins of rat kidney (ROMK1) in response to ATP were performed with a time resolution of about 100 ms in physiological buffer. Fifth, the AFM continuously followed dissociation processes of multimeric macromolecules (such as transcription factors) under physiological conditions and, on the basis of individual molecular volume measurements, allowed estimation of the number of monomers in a multimeric complex. Taken together, the AFM offers a wide spectrum of novel approaches for the experimental nephrolog

ISSN:1420-4096    

DOI:10.1159/000174061

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Epithelia, like other vertebrate cells, are equipped with an extensive network of signaling pathways, involved in the regulation of a large variety of distinct cellular functions. Amongst many the intracellular Ca2+ [Ca2+]i signal is the most common one. On the one hand, [Ca2+]i is involved in regulation functions of general cell physiology, such as the control of cell volume, cell growth or differentiation. On the other hand, [Ca2+]i controls epithelia-specific functions like the regulation of transepithelial solute transport. This short overview addresses the various aspects of Ca2+ signaling in epithelia. It is emphasized that [Ca2+]i is a spatially restricted signal, permitting the distinct regulation of one cellular response. Evidence will be discussed indicating that the functional epithelial polarity is paralleled by polarized membrane receptors and polarized [Ca2+]i signals, regulating the apical and basolateral membranes differentially.

ISSN:1420-4096    

DOI:10.1159/000174062

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Renal proximal tubular Na/phosphate cotransport is the key target in the control of renal phosphate handling. Using molecular tools for the type II Na/phosphate cotransporter, it could be documented that altered brush border membrane phosphate transport reflects a state of altered brush border expression of the specific transporter molecule. This alteration is either the consequence of specific membrane insertion/retrieval processes and/or reflects states of altered synthesisdegradation of the transporter.

ISSN:1420-4096    

DOI:10.1159/000174063

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

The availability of cloned transport molecules achieved by efforts in expression cloning has allowed their electrophysiological analysis in the Xenopus oocyte expression system. We describe the electrogenic uptake of various substrates by their corresponding transport molecules originally expressed in brush border membranes of proximal tubules. The functional properties of the following transport molecules are discussed: the sodium-coupled glucose transporter, the sodium-coupled phosphate transporter, the sodium-coupled sulfate transporter and the sodium-independent transporter of neutral and dibasic amino acids. Additionally, functional consequences of naturally occurring disease-causing mutations in some of these transport molecules are described.

ISSN:1420-4096    

DOI:10.1159/000174064

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Blood pressure regulation is an integrated physiological phenomenon known to be influenced by many biological processes and by a variety of environmental factors. Epidemiological studies nevertheless suggest that up to 30% of the variation in blood pressure could be due to genetic factors. Thus, mutations in genes that control blood pressure may be the underlying cause of essential hypertension. Arterial blood pressure is critically dependent on the sodium balance and the regulation of renal sodium excretion is one of the most important homeostatic functions of the body. The identification of genes encoding proteins that transport Na+ across cells of the kidney tubules and of those regulating the activity of these sodium-transporting proteins will therefore bring further insights into the pathophysiology of salt-sensitive hypertension.

ISSN:1420-4096    

DOI:10.1159/000174065

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

The endothelium lines all vessels of the body and is the most important structure for communication between the flowing blood and the vessel wall. Healthy endothelium has antiadhesive and antithrombotic properties and is crucial for maintaining blood flow. It serves as a permeability barrier and prevents noxious agents from entering the vessel wall. Endothelial cells have secretory functions and secrete vasorelaxant substances. Therefore, functioning endothelium sustains the homoeostasis of the vessel wall. Endothelial functions are impaired by risk factors for cardiovascular disease such as hypertension, hyperlipidemia and hyperglycemia. Hypertension leads to decreased generation of nitric oxide in endothelial cells, thereby diminishing their vasorelaxant properties. Hypertension also contributes to an increase in endothelial cell permeability leading to intimal edema. Thirdly, hypertension increases the expression of adhesion molecules and increases the adherence of leukocytes to the vessel wall. Hence, hypertension directly contributes to the pathological alterations of the endothelium and it seems that these effects initiate and accelerate the pathogenesis of chronic vascular disease.

ISSN:1420-4096    

DOI:10.1159/000174066

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Recent studies have shown that enhanced Na/H exchanger activity, a frequently observed abnormality in essential hypertension, persists in Epstein-Barr-virus-immortalised lymphoblasts from afflicted patients. This phenomenon is associated with an enhanced proliferation of these cell lines. Studies have ruled out structural changes in the Na/H exchanger protein, but demonstrated a distinct enhancement of intracellular signal transduction in these cell lines. The ultimate cause can be assigned to an obviously genetically fixed increased reactivity of pertussis-toxin-sensitive G proteins, which can easily explain the increased formation of intracellular second messengers, enhanced Ca2+ signals, and enhanced proliferation of these cell lines. Thus, hypertension in the subset of patients with enhanced Na/H exchanger activity could be caused by increased G protein reactivity.

ISSN:1420-4096    

DOI:10.1159/000174067

出版商:S. Karger AG    

年代:1996

数据来源: Karger