The control of calcium current reactivation by catecholamines and acetylcholine in single guinea-pig ventricular myocytes

The time course of reactivation of the calcium current in isolated single cardiac cells is complex. The rising phase is sigmoid and there is an overshoot. Catecholamines increase the initial rate of reactivation but reduce or abolish the overshoot. This combination of effects results in a 'crossover', so that the net effect of adrenaline depends on the pulse interval used. Acetylcholine not only reduces the current amplitude, it also substantially slows recovery. At short intervals the effect of acetylcholine is therefore very large. Agents that increase intracellular cyclic AMP levels affect the amplitude of the current but do not have a large effect on the reactivation time course. It is suggested that the autonomic transmitters exert their effects by controlling the local calcium concentration near the inner surface of the channels. This is supported by the fact that there are natural variations in reactivation time course between different cells and that these are correlated with their calcium loading, as judged by other electrophysiological criteria, such as the speed of calcium current inactivation and the presence of the calcium-dependent slow inward current.     

D-Alanylation of Lipoteichoic Acids Confers Resistance to Cationic Peptides in Group B Streptococcus by Increasing the Cell Wall Density

Cationic antimicrobial peptides (CAMPs) serve as the first line of defense of the innate immune system against invading microbial pathogens. Gram-positive bacteria can resist CAMPs by modifying their anionic teichoic acids (TAs) with D-alanine, but the exact mechanism of resistance is not fully understood. Here, we utilized various functional and biophysical approaches to investigate the interactions of the human pathogen Group B Streptococcus (GBS) with a series of CAMPs having different properties. The data reveal that: (i) D-alanylation of lipoteichoic acids (LTAs) enhance GBS resistance only to a subset of CAMPs and there is a direct correlation between resistance and CAMPs length and charge density; (ii) resistance due to reduced anionic charge of LTAs is not attributed to decreased amounts of bound peptides to the bacteria; and (iii) D-alanylation most probably alters the conformation of LTAs which results in increasing the cell wall density, as seen by Transmission Electron Microscopy, and reduces the penetration of CAMPs through the cell wall. Furthermore, Atomic Force Microscopy reveals increased surface rigidity of the cell wall of the wild-type GBS strain to more than 20-fold that of the dltA mutant. We propose that D-alanylation of LTAs confers protection against linear CAMPs mainly by decreasing the flexibility and permeability of the cell wall, rather than by reducing the electrostatic interactions of the peptide with the cell surface. Overall, our findings uncover an important protective role of the cell wall against CAMPs and extend our understanding of mechanisms of bacterial resistance.     

Heat acclimation: cardiac performance of isolated rat heart

Cardiac performance was studied in the isolated perfused hearts of rats heat acclimated at 34 degrees C (AC) and their age-matched controls (C). The pressure-volume curves during isovolumetric conditions showed a shift to the right in AC compared with C hearts. At similar left ventricular (LV) volumes end-diastolic and peak systolic pressures of AC hearts were lower, but no difference was observed in the maximal pressure developed at the highest LV volumes measured. In both C and AC hearts the developed force decreased as pacing rate increased. AC and C heart responses were the same up to 250 pulses/min. At higher frequencies the amplitude of the developed force of AC hearts was smaller than that of the controls. In accordance the tension produced by very early premature beat reduced in AC compared with C hearts. Since no hypertrophy was observed in AC hearts, it is concluded that heat acclimation results in a change in the intrinsic properties of the AC hearts exhibited by increased compliance, reduced chamber stiffness, and a decrease in the tension developed for each volume load. It is also suggested that at a high beating rate AC hearts fail to restitute its contractility as quickly as C hearts.