Reinventing the wheel: comparison of two wheel cage styles for assessing mouse voluntary running activity.

Voluntary wheel cage assessment of mouse activity is commonly employed in exercise and behavioral research. Currently, no standardization for wheel cages exists resulting in an inability to compare results among data from different laboratories. The purpose of this study was to determine whether the distance run or average speed data differ depending on the use of two commonly used commercially available wheel cage systems. Two different wheel cages with structurally similar but functionally different wheels (electromechanical switch vs. magnetic switch) were compared side-by-side to measure wheel running data differences. Other variables, including enrichment and cage location, were also tested to assess potential impacts on the running wheel data. We found that cages with the electromechanical switch had greater inherent wheel resistance and consistently led to greater running distance per day and higher average running speed. Mice rapidly, within 1-2 days, adapted their running behavior to the type of experimental switch used, suggesting these running differences are more behavioral than due to intrinsic musculoskeletal, cardiovascular, or metabolic limits. The presence of enrichment or location of the cage had no detectable impact on voluntary wheel running. These results demonstrate that mice run differing amounts depending on the type of cage and switch mechanism used and thus investigators need to report wheel cage type/wheel resistance and use caution when interpreting distance/speed run across studies. NEW & NOTEWORTHY The results of this study highlight that mice will run different distances per day and average speed based on the inherent resistance present in the switch mechanism used to record data. Rapid changes in running behavior for the same mouse in the different cages demonstrate that a strong behavioral factor contributes to classic exercise outcomes in mice. Caution needs to be taken when interpreting mouse voluntary wheel running activity to include potential behavioral input and physiological parameters.

Identification of the t-type calcium channel (Ca(v)3.1d) in developing mouse heart.

During cardiac development, there is a reciprocal relationship between cardiac morphogenesis and force production (contractility). In the early embryonic myocardium, the sarcoplasmic reticulum is poorly developed, and plasma membrane calcium (Ca(2+)) channels are critical for maintaining both contractility and excitability. In the present study, we identified the Ca(V)3.1d mRNA expressed in embryonic day 14 (E14) mouse heart. Ca(V)3.1d is a splice variant of the alpha1G, T-type Ca(2+) channel. Immunohistochemical localization showed expression of alpha1G Ca(2+) channels in E14 myocardium, and staining of isolated ventricular myocytes revealed membrane localization of the alpha1G channels. Dihydropyridine-resistant inward Ba(2+) or Ca(2+) currents were present in all fetal ventricular myocytes tested. Regardless of charge carrier, inward current inactivated with sustained depolarization and mirrored steady-state inactivation voltage dependence of the alpha1G channel expressed in human embryonic kidney-293 cells. Ni(2+) blockade discriminates among T-type Ca(2+) channel isoforms and is a relatively selective blocker of T-type channels over other cardiac plasma membrane Ca(2+) handling proteins. We demonstrate that 100 micromol/L Ni(2+) partially blocked alpha1G currents under physiological external Ca(2+). We conclude that alpha1G T-type Ca(2+) channels are functional in midgestational fetal myocardium.

Isolation and characterization of the products of anoxic irradiation of d(CpGpTpA).

An improved method for separating the products of DNA oligomers irradiated in aqueous solution has been devised. Altogether 39 products were isolated from the tetramer d(CpGpTpA) X-irradiated in dilute anoxic solution. Of these, 16, including most of the major products, were identified through the use of proton nmr spectroscopy. The identified products fall into four categories: (1) base products, (2) strand scission products, (3) base modifications and (4) tandem lesion. A tandem lesion in which the methyl carbon atom of thymine is covalently linked to the guanine C8 carbon atom was produced in larger yield than any of the simple base modifications.

Effects of mechanical interaction between two rabbit cardiac muscles connected in parallel.

The hypothesis that myocardium mechanical inhomogeneity produces a substantial effect on mechanical function was tested. Muscle inhomogeneity was studied in isolated papillary muscles or trabeculae excised from rabbit right ventricle and connected in a parallel duplex. Each muscle was placed in a separate perfusion bath. One end of each muscle was fastened to an individual force transducer and the other to the common lever of a servomotor. This arrangement allowed both muscles, being excited independently, to pull jointly a load applied to the lever. Separate electrodes for each perfusion bath allowed to stimulate muscles with a time delay. Tension developed in the individual muscles and their interaction were studied. Developed tension was critically dependent on the timing and sequence of excitation. Using mathematical modeling, patterns of tension distribution experimentally observed in parallel duplexes were simulated. These results suggest that changes both in Ca(2+) transients and in the time course of Ca(2+)-troponin complexion due to the duplexed muscles interaction offset the effect of mechanical inhomogeneity.