ISSN:0009-7330    

出版商:OVID    

年代:2003

数据来源: OVID

ISSN:0009-7330    

出版商:OVID    

年代:2003

数据来源: OVID

ISSN:0009-7330    

出版商:OVID    

年代:2003

数据来源: OVID

ISSN:0009-7330    

出版商:OVID    

年代:2003

数据来源: OVID

ISSN:0009-7330    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Na+influx viaINaduring cardiac action potentials can raise bulk [Na+]iby 10 to 15 &mgr;mol/L. However, larger rises in submembrane [Na+] ([Na+]sm) local to Na+-Ca2+exchangers (NCX) could enhance Ca2+influx via NCX (and Ca2+-induced Ca2+release). We tested whetherINacould increase [Na+]sm, using NCX current (INCX) as a biosensor in rabbit ventricular myocytes (with [Ca2+]ibuffered, [Na+]i=10 mmol/L, and other currents blocked). We measuredINCXas early as 5 ms afterINa. PriorINaactivation did not affectINCXat physiological membrane potentials (Em=−100 to +50 mV), but for Em>+50 mV (whereINCXis especially sensitive to [Na+]i),INCXshifted outward. At 5 ms and +100 mV,INashiftedINCXoutward by 0.23 A/F (corresponding to &Dgr;[Na+]sm=0.24 mmol/L). The effect ofINadissipated with a time constant of ≈15 ms. Thus, the impact ofINaon NCX is almost undetectable at physiological Emand short lived. This suggests thatINaeffects on excitation-contraction coupling (via outwardINCX) are minimal and limited to early during the action potential. However, local &Dgr;[Na+]smduringINamay be 60 times higher than bulk &Dgr;[Na+]i.

ISSN:0009-7330    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Abstract—This article reviews recent advances in genomics and informatics relevant to cardiovascular research. In particular, we review the status of (1) whole genome sequencing efforts in human, mouse, rat, zebrafish, and dog; (2) the development of data mining and analysis tools; (3) the launching of the National Heart, Lung, and Blood Institute Programs for Genomics Applications and Proteomics Initiative; (4) efforts to characterize the cardiac transcriptome and proteome; and (5) the current status of computational modeling of the cardiac myocyte. In each instance, we provide links to relevant sources of information on the World Wide Web and critical appraisals of the promises and the challenges of an expanding and diverse information landscape.

ISSN:0009-7330    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Abstract—Functional proteome analysis is not restricted to the sequence information but includes the broad spectrum of structural modifications and quantitative changes of proteins to which they are subjected in different tissues and cell organelles and during the development of an organism. Cell biology has provided the means required for the analysis of the composition and properties of purified cellular elements. Subcellular fractionation is an approach universal across all cell types and tissues, including cardiac and vascular system. Subcellular fractionation and proteomics form an ideal partnership when it comes to enrichment and analysis of intracellular organelles and low abundant multiprotein complexes. Subcellular fractionation is a flexible and adjustable approach resulting in reduced sample complexity and is most efficiently combined with high-resolution 2D gel/mass spectrometry analysis as well as with gel-independent techniques. In this study we introduce state of the art subcellular fractionation techniques and discuss their suitability, advantages, and limitations for proteomics research.

ISSN:0009-7330    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Abstract—The impact of common variants in the apolipoprotein gene cluster (APOC3-A4-A5) on prospective coronary heart disease (CHD) risk was examined in healthy UK men. Of the 2808 men followed over 9 years, 187 had a clinically defined CHD event. Examination of 9 single nucleotide polymorphisms (SNPs) in this group revealed that homozygotes forAPOA4S347 had significantly increased risk of CHD [hazard ratio (HR) of 2.07 (95%CI 1.04 to 4.12)], whereas men homozygous forAPOC31100T were protected [HR 0.28 (95%CI 0.09 to 0.87)]. In stepwise multiple regression analysis, after entering all the variants and adjusting for established risk factorsAPOA4T347S alone remained in the model. Using all nine SNPs, the highest risk-estimate haplotypes carriedAPOA4S347 and rare alleles of the two flanking intergenic markers. The protective effect ofAPOC31100T could be explained by negative linkage disequilibrium with these alleles. To determine the association ofAPOA4T347S with apoAIV levels, the relationship was examined in 1600 healthy young European men and women. S347 homozygotes had significantly lower apoAIV plasma levels (13.64±0.59 mg/dL) compared with carriers of the T347 allele (14.90±0.12 mg/dL) (P=0.035). These results demonstrate that genetic variation in and aroundAPOA4, independent of the effects of triglyceride, is associated with risk of CHD and apoAIV levels, supporting an antiatherogenic role for apoAIV.

ISSN:0009-7330    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Abstract—One variant of the long-QT syndrome (LQT3) is caused by mutations in the human cardiac sodium channel gene. In addition to the characteristic QT prolongation, LQT3 carriers regularly present with bradycardia and sinus pauses. Therefore, we studied the effect of the 1795insD Na+channel mutation on sinoatrial (SA) pacemaking. The 1795insD channel was previously characterized by the presence of a persistent inward current (Ipst) at −20 mV and a negative shift in voltage dependence of inactivation. In the present study, we first additionally characterizedIpstover the complete voltage range of the SA node action potential (AP) by measuring whole-cell Na+currents (INa) in HEK-293 cells expressing either wild-type or 1795insD channels.Ipstfor 1795insD channels varied between 0.8±0.2% and 1.9±0.8% of peakINa. Activity of 1795insD channels during SA node pacemaking was confirmed by AP clamp experiments. Next,Ipstand the negative shift were implemented into SA node AP models. The −10-mV shift decreased sinus rate by decreasing diastolic depolarization rate, whereasIpstdecreased sinus rate by AP prolongation, despite a concomitant increase in diastolic depolarization rate. In combination, moderateIpst(1% to 2%) and the shift reduced sinus rate by ≈10%. An additional increase inIpstcould result in plateau oscillations and failure to repolarize completely. Thus, Na+channel mutations displaying anIpstor a negative shift in inactivation may account for the bradycardia seen in LQT3 patients, whereas SA node pauses or arrest may result from failure of SA node cells to repolarize under conditions of extra net inward current.

ISSN:0009-7330    

出版商:OVID    

年代:2003

数据来源: OVID