Increasing extracellular K+ concentration ([K+]o) from 4 to 7-14 mM reduced both tetanic force and resting membrane potential (Em) in isolated slow-twitch soleus and fast-twitch extensor digitorum longus (EDL) muscles of the mouse. The tetanic force-[K+]o relationships showed a greater force loss over 8-11 mM [K+]o in soleus than EDL, mainly because the Em was 2-3 mV less negative at each [K+]o in soleus. The tetanic force-resting Em relationships show that force was reduced in two phases: phase 1 (Em < -60 mV), a 20% force decline in which the relationships superimposed in soleus and EDL, and phase 2 (Em -60 to -55 mV), a marked force decline that was steeper in EDL than soleus. Additionally in phase 2, longer stimulation pulses restored tetanic force; the twitch force-stimulation strength relationship was shifted toward higher voltages; caffeine, a myoplasmic Ca2+ concentration elevator, increased maximum force; and twitch force fell abruptly. We suggest that 1) the K(+)-depressed force is due to reduced Ca2+ release resulting from an altered action potential profile (phase 1) and inexcitable fibers due to an increased action potential threshold (phase 2), and 2) K+ contributes to fatigue in both fast- and slow-twitch muscle when it causes depolarization to about -60 mV.

As ∼80% of diabetic patients die from heart failure, an understanding of diabetic cardiomyopathy is crucial. Mitochondria occupy 35–40% of the mammalian cardiomyocyte volume and supply 95% of the heart's ATP, and diabetic heart mitochondria show impaired structure, arrangement, and function. We predict that bioenergetic inefficiencies are present in diabetic heart mitochondria; therefore, we explored mitochondrial proton and electron handling by linking oxygen flux to steady-state ATP synthesis, reactive oxygen species (ROS) production, and mitochondrial membrane potential (ΔΨ) within rat heart tissues. Sprague-Dawley rats were injected with streptozotocin (STZ, 55 mg/kg) to induce type 1 diabetes or an equivalent volume of saline (control, n = 12) and fed standard rat chow for 8 wk. By coupling high-resolution respirometers with purpose-built fluorometers, we followed Magnesium Green (ATP synthesis), Amplex UltraRed (ROS production), and safranin-O (ΔΨ). Relative to control rats, the mass-specific respiration of STZ-diabetic hearts was depressed in oxidative phosphorylation (OXPHOS) states. Steady-state ATP synthesis capacity was almost one-third lower in STZ-diabetic heart, which, relative to oxygen flux, equates to an estimated 12% depression in OXPHOS efficiency. However, with anoxic transition, STZ-diabetic and control heart tissues showed similar ATP hydrolysis capacities through reversal of the F₁F₀-ATP synthase. STZ-diabetic cardiac mitochondria also produced more net ROS relative to oxygen flux (ROS/O) in OXPHOS. While ΔΨ did not differ between groups, the time to develop ΔΨ with the onset of OXPHOS was protracted in STZ-diabetic mitochondria. ROS/O is higher in lifelike OXPHOS states, and potential delays in the time to develop ΔΨ may delay ATP synthesis with interbeat fluctuations in ADP concentrations. Whereas diabetic cardiac mitochondria produce less ATP in normoxia, they consume as much ATP in anoxic infarct-like states.

1 We have used fluorescence confocal laser scanning microscopy to attain the three-dimensional (3-D) microstructure of perimysial collagen fibres over the range of sarcomere lengths (1.9–2.3 μm) in which passive force of cardiac muscle increases steeply. 2 A uniaxial muscle preparation (right ventricular trabecula of rat) was used so that the 3-D collagen configuration could be readily related to sarcomere length. Transmission electron microscopy showed that these preparations were structurally homologous to ventricular wall muscle. 3 Trabeculae were mounted on the stage of an inverted microscope and fixed at various sarcomere lengths. After a trabecula was stained with the fluorophore Sirius Red F3BA and embedded in resin, sequential optical sectioning enabled 3-D reconstruction of its perimysial collagen fibres. The area fraction of these fibres, determined from the cross-sections of seven trabeculae, was 10.5 ± 3.9 % (means ± s.d.). 4 The reconstructed 3-D images show that perimysial collagen fibres are wavy (as distinct from coiled) cords which straighten considerably as the sarcomere length is increased from 1.85 ± 0.06 μm (near-resting length) to 2.3 ± 0.04 μm (means ± s.d., n= 4). These observations are consistent with the notion that the straightening of these fibres is responsible for limiting extension of the cardiac sarcomere to a length of ≈2.3 μm.

The energy flux of rat, guinea pig, and cat papillary muscles was measured myothermically under resting, isometric, and isotonic conditions at 27 degrees C. Resting heat rate was highest in the smallest species and declined with body size. The slope of the isometric heat-stress relationship was constant across species, whereas the stress-independent heat component was least for rat muscles. The shape of the load enthalpy relationship was similar across species. Maximum mechanical efficiency, work-enthalpy, occurred with lighter loads than for skeletal muscle (approximately 0.2 Po). Rat muscle had the smallest enthalpy per beat and the highest active mechanical efficiency, but this advantage was nullified by the higher basal heat rate. The myothermic data are compared with cardiac oxygen consumption values in the literature and it is concluded, contrary to the deductions of common dimensional arguments, that cardiac energy expenditure across species is not directly proportional to heart rate. Reasons for this discrepancy are considered together with the likely contribution of cardiac metabolism (EH) to total body metabolism (EB). It seems likely that smaller species have lower EH/EB.