Essential Role of the m2R-RGS6-IKACh Pathway in Controlling Intrinsic Heart Rate Variability

Normal heart function requires generation of a regular rhythm by sinoatrial pacemaker cells and the alteration of this spontaneous heart rate by the autonomic input to match physiological demand. However, the molecular mechanisms that ensure consistent periodicity of cardiac contractions and fine tuning of this process by autonomic system are not completely understood.Here we examined the contribution of the m₂R-I_KACh intracellular signaling pathway, which mediates the negative chronotropic effect of parasympathetic stimulation, to the regulation of the cardiac pacemaking rhythm. Using isolated heart preparations and single-cell recordings we show that the m₂R-I_KACh signaling pathway controls the excitability and firing pattern of the sinoatrial cardiomyocytes and determines variability of cardiac rhythm in a manner independent from the autonomic input. Ablation of the major regulator of this pathway, Rgs6, in mice results in irregular cardiac rhythmicity and increases susceptibility to atrial fibrillation. We further identify several human subjects with variants in the RGS6 gene and show that the loss of function in RGS6 correlates with increased heart rate variability. These findings identify the essential role of the m₂R-I_KACh signaling pathway in the regulation of cardiac sinus rhythm and implicate RGS6 in arrhythmia pathogenesis.     

Evolution of resource specialisation in competitive metacommunities

Spatial environmental heterogeneity coupled with dispersal can promote ecological persistence of diverse metacommunities. Does this premise hold when metacommunities evolve? Using a two‐resource competition model, we studied the evolution of resource‐uptake specialisation as a function of resource type (substitutable to essential) and shape of the trade‐off between resource uptake affinities (generalist‐ to specialist‐favouring). In spatially homogeneous environments, evolutionarily stable coexistence of consumers is only possible for sufficiently substitutable resources and specialist‐favouring trade‐offs. Remarkably, these same conditions yield comparatively low diversity in heterogeneous environments, because they promote sympatric evolution of two opposite resource specialists that, together, monopolise the two resources everywhere. Consumer diversity is instead maximised for intermediate trade‐offs and clearly substitutable or clearly essential resources, where evolved metacommunities are characterised by contrasting selection regimes. Taken together, our results present new insights into resource‐competition‐mediated evolutionarily stable diversity in homogeneous and heterogeneous environments, which should be applicable to a wide range of systems.     

Biotite and microcline as potassium sources in ectomycorrhizal and non-mycorrhizal Pinus sylvestris seedlings

 The aim of this study was to investigate the role of plants colonised by two ectomycorrhizal fungi, Paxillus involutus and Suillus variegatus, in mobilising potassium (K) from biotite and microcline, two minerals common in acid to medium-acid bedrock. This was carried out in a 33-week pot study with seedlings of Pinus sylvestris growing in symbiosis with the fungi, where no K was added or where K was added in the form of biotite or microcline. The mineral additions were similar to those found in natural soils. All seedlings, including non-mycorrhizal, were able to access the K in biotite, leading to stimulated growth and K uptake relative to controls. Microcline addition induced growth depression in all seedlings except those colonised by P. involutus, which were stimulated. The soil solution from S. variegatus-colonised seedlings grown with biotite had higher concentrations of citric and oxalic acid. Citric acid concentration was positively correlated to the fungal biomass (ergosterol) in the soil, as well as to the foliar K in S. variegatus-colonised seedlings. Seedlings growing without K addition had low K concentrations in the shoot. Magnesium (Mg) concentrations were enhanced in seedlings with severe K shortage, indicating that Mg can substitute for K, while calcium concentrations did not vary significantly. Accepted: 18 January 1999     

Postnatal deficiency of essential fatty acids in mice results in resistance to diet-induced obesity and low plasma insulin during adulthood

Our objective was to investigate the long-term metabolic effects of postnatal essential fatty acid deficiency (EFAD). Mouse dams were fed an EFAD diet or an isoenergetic control diet 4 days before delivery and throughout lactation. The pups were weaned to standard diet (STD) and were later subdivided into two groups: receiving high fat diet (HFD) or STD. Body composition, energy expenditure, food intake and leptin levels were analyzed in adult offspring. Blood glucose and plasma insulin concentrations were measured before and during a glucose tolerance test. EFAD offspring fed STD were leaner with lower plasma leptin and insulin concentrations compared to controls. EFAD offspring fed HFD were resistant to diet-induced obesity, had higher energy expenditure and lower levels of plasma leptin and insulin compared to controls. These results indicate that the fatty acid composition during lactation is important for body composition and glucose tolerance in the adult offspring.     

Growth hormone receptor deficiency in mice results in reduced systolic blood pressure and plasma renin, increased aortic eNOS expression, and altered cardiovascular structure and function

To study the role of the growth hormone receptor (GHR) in the development of cardiovascular structure and function, female GHR gene-disrupted or knockout (KO) and wild-type (WT) mice at age 18 wk were used. GHR KO mice had lower plasma renin levels (12 +/- 2 vs. 20 +/- 4 mGU/ml, P < 0.05) and increased aortic endothelial NO synthase (eNOS) expression (146%, P < 0.05) accompanied by a 25% reduction in systolic blood pressure (BP, 110 +/- 4 vs. 147 +/- 3 mmHg, P < 0.001) compared with WT mice. Aldosterone levels were unchanged, whereas the plasma potassium concentration was elevated by 14% (P < 0.05) in GHR KO. Relative left ventricular weight was 14% lower in GHR KO mice (P < 0.05), and cardiac dimensions as analyzed by echocardiography were similarly reduced. Myograph studies revealed a reduced maximum contractile response in the aorta to norepinephrine (NE) and K(+) (P < 0.05), and aorta media thickness was decreased in GHR KO (P < 0.05). However, contractile force was normal in mesenteric arteries, whereas sensitivity to NE was increased (P < 0.05). Maximal acetylcholine-mediated dilatation was similar in WT and GHR KO mice, whereas the aorta of GHR KO mice showed an increased sensitivity to acetylcholine (P < 0.05). In conclusion, loss of GHR leads to low BP and decreased levels of renin in plasma as well as increase in aortic eNOS expression. Furthermore, GHR deficiency causes functional and morphological changes in both heart and vasculature that are beyond the observed alterations in body size. These data suggest an important role for an intact GH/IGF-I axis in the maintenance of a normal cardiovascular system.     

A simple algal production system designed to utilize the flashing light effect

Arrays of foils similar in design to airplane wings have been placed in an algal culture flume to create systematic mixing. Vortices are produced in the culture due to the pressure differential created as water flows over and under the foils. In a flume having a flow rate of 30 cm/s, the foil arrays produced vortices with rotation rates of ca. 0.5-1.0 Hz. This rotation rate is satisfactory to take advantage of the flashing light effect if the culture is sufficiently dense. Solar energy conversion efficiencies in an experimental culture of P. tricornutum increased 2.2-2.4 fold with the foil arrays in place versus controls with no foil arrays and solar energy conversion efficiencies averaged 3.7% over a three-month period. Five-day running means of solar energy conversion efficiencies reached as high as 10% during the three-month period. The use of foil arrays appears to be an effective and inexpensive way to utilize the flashing light effect in a dense algal culture system.     

Vesicular dopamine release elicits an inhibitory postsynaptic current in midbrain dopamine neurons

Synchronous activation of dopamine neurons, for instance upon presentation of an unexpected rewarding stimulus, results in the release of dopamine from both terminals in projection areas and somatodendritic sites within the ventral midbrain. This report describes an inhibitory postsynaptic current (IPSC) that was elicited by dopamine in slices from mouse midbrain. The IPSC was tetrodotoxin sensitive, calcium dependent, and blocked by a D2 receptor antagonist. Inhibition of monoamine transporters prolonged the IPSC, indicating that the time course of dopamine neurotransmission is tightly regulated by reuptake. Changing the stimulus intensity altered the amplitude but not the time course of the IPSC, whose onset was faster than could be reproduced with iontophoresis. The results indicate a rapid rise in dopamine concentration at the D2 receptors, suggesting that dopamine that is released by a train of action potentials acts in a localized area rather than in a manner consistent with volume transmission.     

Apatite as a P source in mycorrhizal and non-mycorrhizal Pinus sylvestris seedlings

The objectives of the study are firstly to test the ability of ectomycorrhizal pine seedlings to use apatite as a P source in comparison with non-mycorrhizal pine seedlings and secondly, to determine if there is a relation between exudation of organic acids and the ability to use apatite as a P source. Non-mycorrhizal Pinus sylvestris (L.) seedlings and seedlings ectomycorrhizal with 4 different isolates of ectomycorrhizal fungi were grown for 220 days in sand/peat filled pots with apatite (Ca₅(F,OH)(PO₄)₃) as the sole P source. In an additional experiment, non-mycorrhizal Pinus sylvestris (L.) seedlings and seedlings ectomycorrhizal with 2 different isolates of ectomycorrhizal fungi were grown without any P source for 250 days. All other nutrients were supplied in a balanced nutrient solution.Ectomycorrhizal seedlings grew less than non-mycorrhizal seedlings but ectomycorrhizal seedlings produced a large external mycelium not included in the biomass estimates. All seedlings in the present study had low shoot:root ratios compared to seedlings growing under optimal conditions. All seedlings grown with apatite as P source had higher foliar P concentrations (0.71–2.11 mg/g) than seedlings growing without any P source (0.57–0.75 mg/g) indicating a significant ability to use apatite as a P source. Seedlings colonized by Suillus variegatus and Paxillus involutus had higher concentrations and total contents of P in shoots compared with non-mycorrhizal seedlings, indicating significant improvement of P uptake by these fungi in comparison with non-mycorrhizal seedlings or seedlings colonized Piloderma croceum.No clear relationship between exudation of organic acids and uptake of P was found. Seedlings colonized by S. variegatus reduced the pH of the soil more than seedlings colonized by P. involutus or non-mycorrhizal seedlings. It is suggested that S. variegatus colonization improves the P uptake by reducing the pH of the soil while P. involutus improves P uptake by having a greater ability to absorb dissolved phosphate than non-mycorrhizal roots or roots colonized by the other fungi used in the study.