Calcium induced contracture stimulates Na,K-pump rate in isolated sheep cardiac Purkinje fibers

By keeping intracellular Na+ (aiNa) low, the Na,K-pump can prevent Ca2+ overload of cardiomyocytes. We therefore examined whether Ca2+ stimulates Na,K-pump activity in sheep cardiac Purkinje fibers. By removing Ca2+, Mg2+ and K+, the fibers depolarized and aiNa rose to 70 mM. After addition of 6 mM Mg2+ and lowering extracellular Na2+ to 29 mM, 30mM Rb+ was added, and over 10-15 min aiNa recovered to 3-7 mM. Two load-recovery cycles were conducted in 10 fibers. During one of the cycles Ca2+ (0.1-1.0 mM) was added before Rb+, causing a contracture. During recovery aiNa fell faster during Ca2+ contracture than in control cycles. Between 30 and 20 mM the rates were -10.0+/-1.6 and -5.4+/-0.6 mM/min, respectively (P<0.05). In Ca2+-exposed fibers tension fell almost parallel with aiNa. Na, K-pump reactivation caused membrane potential (Vm) to hyperpolarize transiently to -70 mV. Ca2+ did not affect membrane conductance. For a given aiNa during reactivation, Vm was more negative during Ca2+ contracture and depolarized faster (P<0.05). Intracellular pH (pHi) fell from 7.11+/-0.05 to 6.92+/-0.08 (n.s.) during control load-recovery cycles and was 6.83+/-0.14 at the end of the Ca2+ cycles. ATP content of the fibers did not change significantly through two complete load-recovery cycles, but creatine phosphate (CrP) fell by about 40%. By fitting the data to a model incorporating the Hill equation we show that during Ca2+-induced contracture maximum Na,K-pump rate (Vmax) was increased by about 40% and aiNa that causes 50% pump activation (k0.5) was lowered from 21. 2+/-1.6 to 15.5+/-1.4 mM.     

Preparation and structure of the system (Na1−xLax) (Nb1−(2x_3)Mg2x_3)O3 with x = 0.51, 0.50, 0.435 and 0.4275

Abstracts are not published in this journal This revised version was published online in November 2006 with corrections to the Cover Date.     

Several parameters of the state of the nervous, immune and endocrine systems in newborn rats exposed to irradiation during the preimplantation period of embryogenesis]

About a decade ago the introduction of predictive testing for Huntington's disease (HD) was an important milestone in medical history. The aim of the present paper concerning predictive DNA-testing for HD is fourfold. First of all it describes the professional challenge of elaborating an adequate test protocol and of permanently using a multidisciplinary approach to deal with predictive test requests. Secondly the paper is aimed at unraveling the factors that play a part in uptake and decision making regarding predictive testing. Hereby the Health Belief Model is used as a framework for understanding differences between tested and untested persons. Thirdly the impact of the test result on psychological well-being is reviewed. Finally this paper assesses the utilisation of prenatal diagnosis after predictive testing for HD and reflects on the psychological and ethical implications of different types of prenatal tests, including preimplantation genetic diagnosis.     

Genetic heterogeneity of adrenocorticotropin (ACTH) resistance syndromes: identification of a novel mutation of the ACTH receptor gene in hereditary glucocorticoid deficiency

Hereditary primary adrenal insufficiency syndromes due to ACTH resistance include hereditary glucocorticoid deficiency (HGD) and Allgrove's syndrome (AS). Patients with both conditions present in childhood with failure to thrive, weakness, and fatigue or adrenal crisis; patients with AS in addition have alacrima and achalasia (triple A syndrome). We studied four kindreds with HGD and four kindreds with AS for abnormalities of the ACTH receptor (ACTHR) gene. The ACTHR coding sequence in all AS kindreds and two HGD kindreds was normal. Analysis of the ACTHR gene of the proband in one of the HGD kindreds showed him to be homozygous for the previously described G221T transition causing a Ser74Ile substitution of the protein, which has been shown to inactivate the ACTHR in signal transduction. The proband in another HGD kindred was found to be a compound heterozygote with the G221T transition in one allele and a novel C818A transition in the other allele of ACTHR. The C818A transition caused the substitution of the highly conserved Pro273 by His in the receptor protein. In vitro expression of the mutated ACTHR in mouse melanoma M3 cells showed that at a medium ACTH concentration of 3 nM, cells transfected with the wild-type ACTHR produced twofold and threefold, respectively, of the amount of intracellular cAMP when compared to cells transfected with the ACTHR carrying the Pro273His and the Ser74Ile mutation, respectively, confirming that HGD in this kindred is caused by loss-of-function mutations of the ACTHR. These results showed that the genetic cause of the ACTH-resistant syndromes is heterogeneous.