Society of General Physiologists series最新文献_第6页

Altered calcium currents in human hypokalemic periodic paralysis myotubes expressing mutant L-type calcium channels. 表达突变l型钙通道的人类低钾性周期性麻痹肌管中钙电流的改变。

Society of General Physiologists series Pub Date : 1995-01-01

F Lehmann-Horn, I Sipos, K Jurkat-Rott, R Heine, H Brinkmeier, B Fontaine, L Kovacs, W Melzer

{"title":"Altered calcium currents in human hypokalemic periodic paralysis myotubes expressing mutant L-type calcium channels.","authors":"F Lehmann-Horn, I Sipos, K Jurkat-Rott, R Heine, H Brinkmeier, B Fontaine, L Kovacs, W Melzer","doi":"","DOIUrl":"","url":null,"abstract":"In a genome-wide search, linkage of hypokalemic periodic paralysis (HypoPP), a muscle disease with autosomal dominant inheritance, to chromosome 1q31-32 and cosegregation with the gene encoding the L-type calcium channel/DHP receptor alpha 1 subunit has been reported (Fontaine et al., 1994). Here we show the extended haplotypes of a large HypoPP family who made the detection of the gene product possible. Sequencing of cDNA synthesized from RNA isolated from muscle specimens of two affected family members revealed a G-to-A transition of nucleotide 3716. This base exchange predicts a substitution of histidine for arginine 1239 located in segment IVS4 of the channel protein. By restriction fragment analysis, the mutation was detected in the genomic DNA of all affected family members. Myotubes cultured from the muscle specimens also revealed the mutation suggesting the expression of mutant L-type calcium channel/DHP receptors. Whole-cell recordings of 20 such myotubes showed a strong reduction of the DHP sensitive, slowly activating and inactivating L-type current density to 30% of the current in normal controls. A rapidly activating and inactivating current component (third-type), which is distinct from the also occurring T-type current, was increased. We conclude that HypoPP is a disease of the skeletal muscle DHP receptor. The point mutation in repeat IV of the protein may have a similar effect as drugs which downregulate the channel activity by binding to this domain.","PeriodicalId":76550,"journal":{"name":"Society of General Physiologists series","volume":"50 ","pages":"101-13"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18679439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Molecular genetics of long QT syndrome. 长QT综合征的分子遗传学。

Society of General Physiologists series Pub Date : 1995-01-01

M T Keating

{"title":"Molecular genetics of long QT syndrome.","authors":"M T Keating","doi":"","DOIUrl":"","url":null,"abstract":"In the long QT syndrome (LQT), individuals suffer from syncope, seizures and sudden death due to cardiac arrhythmias, specifically torsade de pointes and ventricular fibrillation. Many of these individuals also have prolongation of the QT interval on electrocardiograms, suggesting abnormal cardiac repolarization. To improve our understanding of the mechanisms underlying LQT and to facilitate presymptomatic diagnosis, we have begun to study families with autosomal dominant LQT. In 1991, we reported tight linkage between the LQT phenotype and the Harvey ras-1 gene (HRAS) in several families of Northern European descent. This discovery localized an LQT gene to chromosome 11p15.5 and made presymptomatic diagnosis in some families possible. In initial experiments, no recombination between HRAS and LQT was observed, making this protoncogene a candidate for LQT. This hypothesis was supported by physiologic data; other investigators had shown that ras proteins modulate cardiac potassium channels and an abnormality of potassium homeostasis could explain LQT. We eliminated HRAS as a candidate, however, by sequencing the coding region in 10 unrelated patients and finding no mutations. This indicated that the LQT locus was nearby, but not HRAS. Autosomal dominant LQT was previously thought to be genetically homogeneous and the first seven LQT families we studied were linked to 11p15.5. In 1992, however, several groups, including my laboratory, identified locus heterogeneity for LQT. Recently we identified a second LQT locus, LQT2, on chromosome 7q35-36. Because several families were unlinked, at least one more LQT locus exists. This degree of heterogeneity presents opportunities. It seems likely, for example, that proteins encoded by distinct LQT genes interact to modulate cardiac repolarization.(ABSTRACT TRUNCATED AT 250 WORDS)","PeriodicalId":76550,"journal":{"name":"Society of General Physiologists series","volume":"50 ","pages":"53-60"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18681371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Potassium channels at nodes of Ranvier: a role in disease? Ranvier淋巴结钾通道:在疾病中的作用?

Society of General Physiologists series Pub Date : 1995-01-01

B L Tempel, W F Hopkins

引用次数: 0

Ion Channels and Genetic Diseases. Proceedings of the Society of General Physiologists 48th Annual Symposium. Woods Hole, Massachusetts, 7-11 September 1994. 离子通道与遗传疾病。综合生理学家学会第48届年会论文集。伍兹霍尔，马萨诸塞州，1994年9月7日至11日。

Society of General Physiologists series Pub Date : 1995-01-01

引用次数: 0

Function and dysfunction of the CFTR chloride channel. CFTR氯离子通道的功能和功能障碍。

Society of General Physiologists series Pub Date : 1995-01-01

J W Hanrahan, J A Tabcharani, F Becq, C J Mathews, O Augustinas, T J Jensen, X B Chang, J R Riordan

引用次数: 0

In vivo sodium channel structure/function studies: consecutive Arg1448 changes to Cys, His, and Pro at the extracellular surface of IVS4. 体内钠通道结构/功能研究:在IVS4细胞外表面，Arg1448连续改变为Cys、His和Pro。

Society of General Physiologists series Pub Date : 1995-01-01

J Wang, V Dubowitz, F Lehmann-Horn, K Ricker, L Ptacek, E P Hoffman

{"title":"In vivo sodium channel structure/function studies: consecutive Arg1448 changes to Cys, His, and Pro at the extracellular surface of IVS4.","authors":"J Wang, V Dubowitz, F Lehmann-Horn, K Ricker, L Ptacek, E P Hoffman","doi":"","DOIUrl":"","url":null,"abstract":"Structure/function relationships in ion channels have been intensively studied through expression of cloned channel subunits in heterologous cellular environments. Considerable information has been gleaned via this approach. However, it is prominent role in vivo: there are many differences between heterologous systems and functioning nerves and muscle in vivo, any one of which is likely to affect channel function. Examples of such variables include glycosylation status of the channel protein, association of muscle-specific membrane or cytoskeletal proteins, and fluctuations of intracellular and extracellular fluid milieu as a function of fluctuating cellular physiology. The identification of single amino acid changes in the voltage-sensitive muscle sodium channel alpha subunit in human and horse genetic disease has permitted a new approach to the study of structure/function relationships in ion channels. Importantly, the interactions between the environment and the abnormal channel can be studied in this in vivo system. Here we report the identification of a novel human sodium channel mutation (R1448P), which causes a severe type of cold-sensitive myotonia and weakness. This patient is compared to a series of other patients having R1448C, and R1448H mutations. We show that the severity of the amino acid change correlates with the severity of clinical symptoms. This data shows that different amino acid replacements in the extracellular surface of domain IV S4 are important for channel function, despite the paucity of heterologous expression data suggesting functional importance of this region. The extreme cold sensitivity of the proline substitution at R1443 suggests that cold temperatures may affect the structural integrity of the channel, and that proline may destabilize the normal structure.","PeriodicalId":76550,"journal":{"name":"Society of General Physiologists series","volume":"50 ","pages":"77-88"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18681373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Molecular biology and hormonal regulation of vertebrate Na+/H+ exchanger isoforms. 脊椎动物Na+/H+交换物异构体的分子生物学和激素调控。

Society of General Physiologists series Pub Date : 1994-05-01 DOI: 10.1159/000173816

L. Counillon, J. Pouysségur

引用次数: 37

Evolution of the G protein alpha subunit multigene family. G蛋白α亚基多基因家族的进化。

Society of General Physiologists series Pub Date : 1994-01-01

T M Wilkie, S Yokoyama

{"title":"Evolution of the G protein alpha subunit multigene family.","authors":"T M Wilkie, S Yokoyama","doi":"","DOIUrl":"","url":null,"abstract":"G protein-mediated signal transduction systems have been identified in a diverse group of eukaryotic organisms, including yeast, plants, Dictyostelium and animals. G protein signaling components have been identified in many of these organisms, from the seven transmembrane domain receptors to distinct alpha, beta and gamma subunits of the heterotrimeric G protein and the intracellular effectors which they regulate. Their broad distribution and sequence conservation implies that genes encoding the components of G protein signaling evolved with early eukaryotes. Their subsequent proliferation among eukaryotic organisms provides an opportunity to study the coevolution of these interacting multigene families. We have focused our interests on G protein alpha subunits, which bind and hydrolyze GTP and interact with receptors and effectors. Gene structure and nucleotide sequence comparisons provided a comprehensive picture of G alpha evolution. Sequence comparisons identified three major groups of G alpha genes, termed the GPA, the G alpha-I and G alpha-II Groups. G alpha genes within the three Groups have evolved at different rates. The GPA Group is primarily composed of G alpha genes from fungi, plants, and slime mold. Within the G alpha-I and G alpha-II Groups, four classes of genes have been identified based upon sequence comparisons and functional similarities; Gi, Gq, G12, and GS. Members of all four classes are expressed in invertebrates and vertebrates but not in other eukaryotes, suggesting that this quartet evolved with metazoan progenitors.","PeriodicalId":76550,"journal":{"name":"Society of General Physiologists series","volume":"49 ","pages":"249-70"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18936434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Relationships of G-protein-coupled receptors. A survey with the photoreceptor opsin subfamily. g蛋白偶联受体的关系。光感受器视蛋白亚家族的研究。

Society of General Physiologists series Pub Date : 1994-01-01

M L Applebury

{"title":"Relationships of G-protein-coupled receptors. A survey with the photoreceptor opsin subfamily.","authors":"M L Applebury","doi":"","DOIUrl":"","url":null,"abstract":"Relationships among the G-protein-coupled receptors were evaluated using several distance matrices with the neighbor-joining method of Saitou and Nei (1987). The relationships generated vary depending upon alignment, length, or region of sequence compared, and the distance matrix used to score similarity. To provide a statistical level of confidence, bootstrap resampling was applied to the analysis of a selection of G-protein-coupled receptors and the subfamily photoreceptor opsins. A general consensus indicates that the opsins behave as a discrete subfamily among the superfamily of G-protein-coupled receptors. Their relationship to other subfamilies remains unresolved. Within the opsin subfamily, the retinochromelike opsins segregate as a discrete group, but are more closely related to the invertebrate than vertebrate opsins. Among vertebrate opsins, the long wavelength cone opsins, the blue/violet opsins, and the rod opsins (including a class of green cone opsins) form distinct subgroups, but their relationships to one another remain unresolved. For this superfamily of receptors, the confidence levels for many branch pairings are low. The application of methods complimentary to those used in this preliminary study will be necessary to resolve questions about appropriate pairing and evolutionary relationships.","PeriodicalId":76550,"journal":{"name":"Society of General Physiologists series","volume":"49 ","pages":"235-48"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18939412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ion channels of microbes. 微生物的离子通道。

Society of General Physiologists series Pub Date : 1994-01-01

Y Saimi, B Martinac, R R Preston, X L Zhou, S Sukharev, P Blount, C Kung

引用次数: 0