The skin is the only organ besides the lungs that is directly exposed to atmospheric oxygen. Apart from the stratum corneum, oxygen is consumed in all layers of the epidermis and dermis. The oxygen demand is partially satisfied by the blood: the dermis exhibits a vasculature that is arranged in two tiers that are parallel to the skin surface. The superficial plexus between the papillary and the upper reticular dermis deep plexus in the lower reticular dermis are connected by perpendicularly orientated communicating vessels. Arcades of capillaries loop upwards into the papillae from the subpapillary plexus (Braverman, 1989). In contrast, the epidermis has no vasculature, but is exposed directly to the atmosphere. As early as 1851, Gerlach was able to show that human skin takes up oxygen from the atmosphere.

It has been known since the nineteenth century that oxygen is taken up by the human skin. With a newly developed sensor it became possible to examine the influence of the vascular supply on the oxygen flux into the skin, tcJ(O2). tcJ(O2) was measured optically by determining the oxygen partial pressure difference, DeltapO2 across a diffusion test membrane, which itself was brought into close contact to the skin surface. Under these conditions DeltapO2 is proportional to the tcJ(O2). The skin perfusion was varied by the application of a hyperemizing ointment on the abdomen of 12 volunteers and by suprasystolic occlusion at the thigh of 20 volunteers. The tcJ(O2) was measured at a temperature of 33 degrees C of the humid skin. It was compared with the skin perfusion monitored by laser Doppler flow, and the capillary oxygen supply measured by transcutaneous partial pressure of oxygen, tcpO2, at an electrode temperature of 37 degrees C. The transcutaneous O2 flux produced a distinct DeltapO2 of 81.8 +/- 8.2 Torr (abdomen) and 72.8 +/- 12.3 Torr (ankle). In hyperemic skin on the abdomen the O2 flux was reduced (DeltapO2 = 57.7 +/- 10.6 Torr). The tcpO2 increased from 8.7 +/- 10.7 to 35.1 +/- 16.9 Torr. During suprasystolic occlusion, DeltapO2 increased by 6.4 +/- 2.3 Torr, whereas laser Doppler flow and tcpO2 decreased significantly. These results indicate that the total oxygen supply of the epidermis and the upper dermis is guaranteed even if the perfusion varies.

Primary cultured myotubes were derived from satellite cells of the diaphragm obtained from both normal mice (RyR3+/+) and mice with a targeted mutation eliminating expression of the type 3 isoform of the ryanodine receptor (RyR3−/−). Using the whole‐cell patch clamp technique, L‐type Ca2+ currents were measured during step depolarizations. Simultaneously, intracellular Ca2+ transients were recorded with the fluorescent indicator dye fura‐2. After correction for non‐instantaneous binding of Ca2+ to the indicator dye and taking into account the dynamics of Ca2+ binding to intracellular constituents, an estimate of the time course of the Ca2+ release rate from the sarcoplasmic reticulum (SR) was obtained. The calculated SR Ca2+ release flux exhibited a marked peak within less than 12 ms after the onset of the voltage‐clamp depolarization and fell rapidly thereafter to a five times lower, almost steady level. It declined rapidly after termination of the depolarization. Signals in normal and RyR3‐deficient myotubes showed no significant difference in the activation of Ca2+ conductance and in amplitude, time course and voltage dependence of the Ca2+ efflux from the SR. In conclusion, the characteristics of voltage‐controlled Ca2+ release reported here are similar to those of mature mammalian muscle fibres. In contrast to differences observed in the contractile properties of RyR3‐deficient muscle fibres, a contribution of RyR3 to excitation‐contraction coupling could not be detected in myotubes.

Malignant hyperthermia (MH) results from a defect of calcium release control in skeletal muscle that is often caused by point mutations in the ryanodine receptor gene (RYR1). In malignant hyperthermia-susceptible (MHS) muscle, calcium release responds more sensitively to drugs such as halothane and caffeine. In addition, experiments on the porcine homolog of malignant hyperthermia (mutation Arg615Cys in RYR1) indicated a higher sensitivity to membrane depolarization. Here, we investigated depolarization-dependent calcium release under voltage clamp conditions in human MHS muscle. Segments of muscle fibers dissected from biopsies of the vastus lateralis muscle of MHN (malignant hyperthermia negative) and MHS subjects were voltage-clamped in a double vaseline gap system. Free calcium was determined with the fluorescent indicator fura-2 and converted to an estimate of the rate of SR calcium release. Both MHN and MHS fibers showed an initial peak of the release rate, a subsequent decline, and rapid turn-off after repolarization. Neither the kinetics nor the voltage dependence of calcium release showed significant deviations from controls, but the average maximal peak rate of release was about threefold larger in MHS fibers.