The effect of external potassium on the elementary conductance of the ACh-induced potassium channel in the sino-atrial node

The mechanism underlying the increase in the potassium conductance of the acetylcholine (ACh)-induced channel on increasing the extracellular potassium concentration (|K|₀) was studied. The relaxation as well as the current fluctuations of the drug-induced current were measured at 3 and 12 mM |K|₀ by conducting voltage clamp experiments in the rabbit sinoatrial node. The following results were obtained:

1. The time constant of relaxation (τ_relax) was not affected by changing |K|₀. In both cases τ_relax was about 130 ms at ?80 mV, 100 ms at ?40 mV and 60 ms at + 20 mV. It is, therefore, unlikely that the increase of the ACh-induced potassium conductance is due to a longer average open time of the drug-operated potassium channels.
2. The chord conductance of the ACh-induced K current was increased by a factor of 1.7 at ?40 mV and by 1.5 at +10 mV on elevation of |K|₀ from 3 to 12 mM.
3. From the relation between the variance of the current fluctuations and the mean amplitude of the current the single channel conductance was determined to be 3.3 pS at 3 mM |K|₀ and 5.9 pS at 12 mM |K|₀, thus γ was increased by a factor of 1.7.
4. From the power density spectrum an increase in the single channel conductance by a factor of 1.8 (at ?40 mV) could be calculated. The corner frequency was not affected.
5. The increase in the potassium conductance, expected from the constant field equation when |K|₀ is increased, agrees well with the experimental results.

     

“Run-down” of the Ca current during long whole-cell recordings in guinea pig heart cells: role of phosphorylation and intracellular calcium

We examined by a statistical approach the decrease of the Ca current (run-down) during long-lasting recordings with the whole-cell patch-clamp technique in guinea pig ventricular myocytes. The results are as follows. (1) Run-down of the Ca current (I _Ca) occurs in three phases (T1–T3). T1 (38±19 min,n=135) and T3 (35±17 min,n=23) are characterized by a slow rate of decay ofI _Ca [90±20 and 60±20 nA·cm^–2·min^–1, respectively]. T1 and T3 are separated by T2 (6±4 min,n=135) during which the current decays quickly [1200±230 nA·cm^–2·min^–1]. Between the onsets of T1 and T3,I _Ca decreases from 11±3 to 3.5±1 A/cm². (2) Normalized current-voltage relationship, reversal potential and voltage-dependencies of steady-state activation and inactivation ofI _Ca are globally shifted toward more negative potentials during the run-down process by 10–15 mV. (3)I _Ca3 measured during T3 retains the pharmacological properties (blockade by D600, NiCl₂ and CoCl₃, increase by isoprenaline and insensitivity to tetrodotoxin) of the originalI _Ca. (4) Intracellular perfusion of the nonhydrolysable ATP analogue AMP-PNP does not prevent the occurrence of T2, suggesting that a phosphorylation-dephosphorylation process is not involved in the fast run-down ofI _Ca. (5) With 0.1 mM EGTA in the pipette, addition of 3 mM ATP significantly prolongsI _Ca survival. No improvements are obtained by increasing the ATP concentration to 10 mM or replacing ATP with creatine phosphate. With 3 mM ATP present, increasing the EGTA concentration to 10–20 mM doublesI _Ca survival time. EGTA alone (10 mM) is less effective than the mixture 3 mM ATP-0.1 mM·EGTA. Intracellular perfusion with a cytoplasmic extract considerably prolongs T2 and the overallI _Ca survival. (6) The results are consistent with the hypothesis that run-down ofI _Ca can partially be explained by a rise in intracellular Ca concentration and a loss of high energy compounds. Beneficial effect of ATP might include an increased capability of the cells to either extrude or sequester intracellular Ca, and a protection against enzymatic proteolysis.Recipient of successive fellowships from the Simone et Cino del Duca and Alexander von Humboldt FoundationsThis work was supported by the Deutsche Forschungsgemeinschaft, SFB 246, Project A1     

Acute hepatitis B virus infection by genotype F despite successful vaccination in an immune-competent German patient.

BACKGROUND: Hepatitis B Virus (HBV) infection is a leading cause of chronic hepatitis and liver cirrhosis worldwide, and efficient protection can usually be achieved by vaccination that is based on recombinant HBsAg protein from HBV genotype A and D. RESULTS: Here we report the case of a fully immune-competent German patient that acquired a symptomatic acute HBV infection during adulthood despite a complete and formally successful vaccination, which had resulted in anti-HBs titers considered protective. Further phylogentic analysis identified an infection with the rare genotype F of HBV, possibly acquired in Spain, without apparent aberrations in the immunodominant 'a' determinant domain of the envelope gene. However, sequence comparisons revealed that all reported genotype F isolates display marked differences from the other genotypes in this domain which serves as an epitope for humoral immune responses. CONCLUSIONS: The rare HBV genotype F, as detected in this immune-competent, previously vaccinated patient, has marked sequences differences in the envelope/polymerase gene. Therefore, current HBV vaccines based on genotype A and D may not result in full protective immunity towards viral strains from genotype F.     

Increased fecal bile acid excretion and changes in the circulating bile acid pool are involved in the hypocholesterolemic and gallstone-preventive actions of psyllium in hamsters

The lipid-lowering effect of psyllium (PSY) is well established. Enhanced fecal bile acid excretion and a stimulation of hepatic bile acid synthesis are discussed as primary mechanisms of this action. To further examine the effect of bile acid excretion and specifically of compositional alterations in the bile acid pool on the cholesterol-lowering and gallstone-preventing action of PSY, male golden Syrian hamsters were fed lithogenic diets containing 5 g/100 g fat, 0.4 g/100 g cholesterol and 0 (control), 4 or 6% PSY or 1% cholestyramine (CHY). PSY significantly lowered plasma total cholesterol and triacylglycerol at a magnitude comparable to that induced by CHY. Although hepatic cholesteryl ester accumulation was completely inhibited by CHY, PSY did not prevent the hepatic storage of esterified cholesterol. PSY and CHY caused distinct alterations in the bile acid profile. PSY caused a selective reduction of taurine-conjugated bile acids, especially of taurochenodeoxycholate. As a result, the glycine:taurine conjugation and the cholate:chenodeoxycholate ratios were significantly higher in PSY-fed hamsters. PSY and CHY normalized the lithogenic index and prevented cholesterol gallstone formation compared with controls. Daily fecal bile acid excretion was approximately 400% greater in hamsters fed 6% PSY, whereas CHY caused an 11-fold increase. Daily neutral sterol excretion did not differ in PSY-fed hamsters but was >100% greater in those fed CHY than in controls. These data emphasize the potent lipid-lowering effect of PSY. Increased fecal bile acid excretion and alterations of the circulating bile acid pool by removal of dihydroxy bile acids (e.g., taurochenodeoxycholate) appear to be main modulators of the hypocholesterolemic action of PSY by leading to an up-regulation of hepatic bile acid synthesis.     

Risk factors for internalizing symptoms: The influence of empathy,theory of mind,and negative thinking processes

Internalizing symptoms such as elevated stress and sustained negative affect can be important warning signs for developing mental disorders. A recent theoretical framework suggests a complex interplay of empathy, theory of mind (ToM), and negative thinking processes as a crucial risk combination for internalizing symptoms. To disentangle these relationships, this study utilizes neural, behavioral, and self-report data to examine how the interplay between empathy, ToM, and negative thinking processes relates to stress and negative affect. We reanalyzed the baseline data of N = 302 healthy participants (57% female, M_age = 40.52, SD_age = 9.30) who participated in a large-scale mental training study, the ReSource project. Empathy and ToM were assessed using a validated fMRI paradigm featuring naturalistic video stimuli and via self-report. Additional self-report scales were employed to measure internalizing symptoms (perceived stress, negative affect) and negative thinking processes (rumination and self-blame). Our results revealed linear associations of self-reported ToM and empathic distress with stress and negative affect. Also, both lower and higher, compared to average, activation in the anterior insula during empathic processing and in the middle temporal gyrus during ToM performance was significantly associated with internalizing symptoms. These associations were dependent on rumination and self-blame. Our findings indicate specific risk constellations for internalizing symptoms. Especially people with lower self-reported ToM and higher empathic distress may be at risk for more internalizing symptoms. Quadratic associations of empathy- and ToM-related brain activation with internalizing symptoms depended on negative thinking processes, suggesting differential effects of cognitive and affective functioning on internalizing symptoms. Using a multi-method approach, these findings advance current research by shedding light on which complex risk combinations of cognitive and affective functioning are relevant for internalizing symptoms.     

Icterus Simplex und Lungentuberkulose

Lung - Es wird über 2 Fälle von Icterus simplex im Verlauf einer Lungentuberkulose berichtet. Die Lebererkrankung führte jedesmal zu erneuter Progredienz der schon in...