Charge movement and depolarization-contraction coupling in arthropod vs. vertebrate skeletal muscle.

Voltage-dependent charge movement has been characterized in arthropod skeletal muscle. Charge movement in scorpion (Centuroides sculpturatus) muscle is distinguishable from that in vertebrate skeletal muscle by criteria of kinetics, voltage dependence, and pharmacology. The function of scorpion charge movement is gating of calcium channels in the sarcolemma, and depolarization-contraction coupling relies on calcium influx through these channels.     

Interferon in essential thrombocythaemia

In the present investigation, 20 patients with ET were treated with recombinant interferon alfa-2c (IFN) for up to 4 years. Initially, IFN was administered subcutaneously at a dosage of 6–45 MU/week. The dosage was adjusted according to individual tolerance and response. The median dose during induction was 20 MU/week, 10 MU/week during the remaining first year, 6 MU/week during the second year and 2 MU/week thereafter.
13 patients (65%) achieved complete remission (platelet count <440/nl), four patients (20%) had partial remission (>440/nl but a reduction by more than 50% of the initial count). The median platelet count remained steady throughout the 4-year period of treatment, in spite of extreme dose reductions. After withdrawal of IFN, however, platelet counts again increased. The white blood cells showed a marked decrease similar to that of platelet counts, whereas the haemoglobin level remained fairly stable. In the bone marrow, a significant decrease in megakaryocyte density and size could be observed.
Concurrently with the improvement of haematological parameters, clinical symptoms improved, but reappeared after withdrawal of IFN. During induction, fever, bone and/or muscle pain, fatigue, lethargy and psychological symptoms were the most prominent side-effects in the majority of patients. In three patients these symptoms led to discontinuation of the treatment. With repeated dose reductions, excellent long-term tolerance was achieved, and during late maintenance treatment the only observed side-effect was an induction of thyroid autoimmunity in three patients.
IFN is an effective, well-tolerated alternative in the long-term treatment of symptomatic ET. However, since withdrawal of IFN leads to recurrence of thrombocytosis, continued treatment is to be recommended.     

Synthesis of sodium channels in the cell bodies of squid giant axons.

Giant axons in squid are formed by fusion of axons from many small cell bodies in the giant fiber lobe (GFL) of the stellate ganglion. Somata of GFL cells in vivo are inexcitable and do not have measurable sodium current (INa) when studied with microelectrode or patch-electrode voltage-clamp techniques. If GFL cells are separated from the giant axons and maintained in primary culture, axon-like INa can be recorded from the somata after several days. Incorporation of Na channels into GFL cell bodies requires protein synthesis, intracellular microtubule-based transport, and the lack of a morphologically defined axon to serve as a sink for channels synthesized in culture.     

Regional distribution of substance P binding sites in the brainstem of the human newborn

The distribution of [³H]substance P ([³H]SP) binding sites in the brainstem of the human was investigated in eleven cases (aged 1 h to 6 months) by in vitro quantitative receptor autoradiography. The binding of [³H]SP to newborn brainstem tissue was found to be saturable (for the eight cases examined,K_d andB_max (M±S.E.M.) were 0.29±0.03 nM and 206±21 fmol/mg tissue, respectively). Competition studies showed unlabeled SP to be the most peptide for displacing [³H]SP binding from tissue sections. The desaturating effect of GTP on the specific binding of [³H]SP was also investigated, but was not found to be significant. Autoradiographic analysis showed that the neurokinin-1 (NK-1)/SP binding sites were widely but unevenly distributed, and that they varied with age. The highest densities of (NK-1)/SP binding sites were observed in the locus coeruleus, olivaris inferior nuclei, raphe magnus and obscurus nuclei, while low to moderate densities were observed in other brainstem structures. These findings support the idea that SP is involved in cardiovascular regulation, and that it may interact with the catecholaminergic and/or serotonergic system.     

Importance of myocardial loading conditions in determining the effects of enflurane on left ventricular function in the intact and isolated canine heart

The effect of enflurane (2% and 4% inspired) on left ventricular (LV) function were examined in chronically instrumented dogs, both intact and after isolation of their hearts and lungs from the systemic circulation. Enflurane in the intact dogs increased heart rate (32 +/- 5% with 2% and 41 +/- 4% with 4%) and elicited striking, dose-dependent decreases in LV stroke shortening (-30 +/- 3% and -41 +/- 4%), the maximum velocity of LV fiber shortening, dD/dt, (-23 +/- 2%) and -40 +/- 2%), LV systolic pressure (-25 +/- 3% and -33 +/- 2%), the maximum rise of LV-pressure, dP/dt (-33 +/- 5% and -55 +/- 3%), and mean aortic pressure (-27 +/- 2% and -37 +/- 1%). However, the LV diastolic performance was impaired little, i.e., even with the higher concentration the LV end-diastolic pressure rose only moderately (32 +/- 4%), while the LV end-diastolic dimensions failed to change significantly; both LV end-diastolic pressure and LV end-diastolic diameter were decreased with the low concentration. Enflurane, after beta-adrenergic blockade alone or after combined beta-adrenergic and cholinergic blockades, or with spontaneous ventilation instead of controlled ventilation, had similar effects. By contrast, in the hearts that were isolated from the systemic circulation and the complex neurohumoral environment, enflurane increased both LV end-diastolic pressure (116 +/- 32% and 492 +/- 58%) and LV end-diastolic diameter (13 +/- 3% and 28 +/- 7%). In intact dogs with aortic pressure artificially increased to conscious control levels, enflurane likewise caused a distinct depression of the LV diastolic performance. Thus, LV systolic unloading appears to be mandatory in order to prevent acute myocardial failure from higher doses of enflurane. The observed changes in LV function with enflurane are largely independent of cardiac rate, adrenergic and cholinergic influences, and the hemodynamic consequences of intermittent positive-pressure ventilation.     

Properties of appropriately and inappropriately expressed sodium channels in squid giant axon and its somata

Neurons that form the giant axons in squid by axonal fusion in the stellate ganglion are inexcitable and do not express functional voltage-controlled sodium (Na) channels in their somata in vivo. These cells do express Na channels in the soma membrane in vitro, however, provided they have been axotomized. We describe here voltage-clamp experiments on the isolated cell bodies maintained in primary culture and on acutely isolated giant axons designed to compare the functional properties of the Na channels expressed inappropriately in the soma with those of channels expressed normally in the axon. Approximately 85% of Na channels in the soma are essentially indistinguishable from those in the giant axon with regard to gating properties and sensitivity to tetrodotoxin or saxitoxin. Thus, the isolated soma is capable of processing Na channels to a state of apparent functional perfection. In addition to these normal Na channels, another type is regularly expressed in the cultured somata. This second type lacks inactivation and is preferentially sensitive to block by cadmium ions, but is otherwise indistinguishable from the more prevalent normal type of channels.