The epidemiology of myasthenia gravis

Neuromuscular junction (NMJ) disorders include several dysfunctions that ultimately lead to muscle weakness. Myasthenia gravis (MG) is the most prevalent NMJ disorder with a highly polymorphic clinical presentation and many different faces. Being an autoimmune disease, MG correlates with the presence of detectable antibodies directed against the acetylcholine receptor, muscle-specific kinase, lipoprotein-related protein 4, agrin, titin, and ryanodine in the postsynaptic membrane at the NMJ. MG has become a prototype serving to understand both autoimmunity and the function of the NMJ better. The aim of this review is to synthesize some of the epidemiological data available. Epidemiological data regarding MG are important for postulating hypotheses regarding its etiology and facilitating the description of MG subtypes. Thus, adequate documentation through broad databases is essential. The incidence and prevalence of MG reported around the globe have been rising steadily and consistently over the past decades. Ethnic aspects, gender-related differences, and environmental risk factors have been described, implying that these might contribute to a specific phenotype, further suggesting that MG may be considered an umbrella term that covers several clinical entities.

Functional organisation of anterior thoracic stretch receptors in the deep-sea isopod Bathynomus doederleini: behavioural, morphological and physiological studies

SUMMARY The relationship between segmental mobility and the organisation of thoracic stretch receptors was examined in the deep-sea isopod Bathynomus doederleini, which shows a developed adaptive behaviour during digging. The movements of segments during digging were analysed from video recordings, which showed that a large excursion occurred in the anterior thoracic segments. Dye-fills of axons revealed four types of thoracic stretch receptor (TSR): an N-cell type (TSR-1), a differentiated N-cell type (TSR-2), a muscle receptor organ (MRO)-type with a long, single receptor muscle (TSR-3) and an MRO-type with a short, single receptor muscle (TSR-4 to TSR-7). Physiologically, TSR-1 and TSR-2 are tonic-type stretch receptors. TSR-3 to TSR-7 show two kinds of stretch-activated responses, a tonic response and a phasico-tonic response in which responses are maintained as long as the stretch stimulus is delivered. Both TSR-2, with a long muscle strand, and TSR-3, with a single, long receptor muscle, have a wide dynamic range in their stretch-activated response. In addition, TSR-2 is controlled by an intersegmental inhibitory reflex from TSR-3. These results suggest that, although TSR-1 has no receptor muscle and TSR-2 has a less-differentiated receptor-like muscle, they are fully functional position detectors of segmental movements, as are the MRO-type receptors TSR-3 to TSR-7.

A mathematical model of the crustacean stretch receptor neuron. Biomechanics of the receptor muscle, mechanosensitive ion channels, and macrotransducer properties

1. A mathematical model of the primary transduction process in a mechanoreceptor, the slowly adapting stretch receptor organ of the crayfish, has been developed taking into account the viscoelastic properties of the accessory structures of the receptor, i.e., the receptor muscle, the biophysical properties of the mechanosensitive channels (MSCs) and the passive electrical properties of the neuronal membrane (leak conductance and capacitative properties). The work is part of an effort to identify and characterize the mechanical and ionic mechanisms in a complex mechanoreceptor. The parameters of the model are based mainly on results of our own experiments and to some extent on results from other studies. The performance of the model has been compared with the performance of the slowly adapting receptor. 2. The model resulted in nonlinear differential equations that were solved by an iterative, fourth order Range-Kutta method. For the calculations of potential, the cell was treated as an idealized spherical body. The extension of the receptor muscle was 0-30%, which is within the physiological limits for this receptor. 3. The mechanical properties of the receptor muscle were modeled by a simple Voigt element (a spring in parallel with a dashpot) in series with a nonlinear spring. This element can describe resonably well the tension development in the receptor muscle at least for large extensions (> 12%). However, for small extensions (< 12%), the muscle seems to be more stiff than for large extensions. 4. The receptor current at different extensions of the receptor was computed using typical viscoelastic parameters for a receptor muscle together with a transformation of muscle tension to tension in the neuronal dendrites and finally the properties of the mechanosensitive channels. The model fit was satisfactory in the high extension range whereas in the low extension range the deviation from the experimental results could be explained partly by insufficient modeling of the nonlinear viscoelastic properties. The voltage dependence of the receptor current was also well predicted by the model. 5. If the parameters of the viscoelastic model were adjusted for each extension so that each tension response closely resembled the experimental values, the fit of the current responses was improved but still deviated from the experimental currents. One factor that might explain the difference is the possibility that the MSCs in the stretch receptor neuron might have intrinsic adaptive properties. Introducing an exponential adaptive behavior of individual MSCs increased the ability of the model to predict the receptor current. 6. The receptor potential was calculated by modeling the neuronal membrane by a lumped leak conductance and capacitance The calculated receptor potential was higher than the experimental receptor potential. However, the fit of the receptor potential was improved substantially by introducing an adaptation of the MSCs as outlined in the preceding paragraph. the remaining discrepancy might be explained by insufficient blocking of K+ channels in the experiment. 7. The model can predict a wide range of experimental data from the slowly adapting stretch receptor neuron including the mechanical response of the receptor muscle, the receptor current and its voltage dependence, and the receptor potential. It also describes accurately the passive electrical properties of the neuronal membrane.

THE MODULATORY EFFECTS OF SEROTONIN, NEUROPEPTIDE F1 AND PROCTOLIN ON THE RECEPTOR MUSCLES OF THE LOBSTER ABDOMINAL STRETCH RECEPTOR AND THEIR EXOSKELETAL MUSCLE HOMOLOGUES

The muscle receptor organ (MRO) of the lobster is a complex proprioceptive system lying in parallel with the axial extensor musculature. Two peripherally located sensory neurones extend stretch-sensitive dendrites into individual receptor muscle strands one tonic (RM1) and one phasic (RM2). Previous studies have shown that the sensitivity of the sensory neurones to passive stretch could be enhanced by serotonin and proctolin. Here we show that the receptor muscles and their exoskeletal muscle homologues are also responsive to serotonin, proctolin and, in addition, to neuropeptide F1 (TNRNFLRF-NH2). Two measures of motor performance were enhanced by all three neurohormones: EJP amplitude and nerve-evoked tension development. Serotonin was the most effective modulator of both tonic and phasic muscles. F1 had powerful effects on the phasic extensor muscle. A low incidence of tonic muscle fibres with synapses responding to the neurohormones suggests that there are distinct populations of synapses: those sensitive to specific modulators and others that are insensitive. These findings, taken together with the enhancing effects of modulation on the primary sensory afferents, suggest that circulating neurohormones may act at multiple loci in the MRO system in a concerted and hormone-specific manner to alter the flow of proprioceptive feedback.