Forcing the issue of physician-assisted suicide. Impact of the Kevorkian case on the euthanasia debate

In this review article we have attempted to provide an overview of the various forms of activity-dependent interactions between motoneurones and muscles and its consequences for the development of the motor unit. During early development the components of the motor unit undergo profound changes. Initially the two cell types develop independently of each other. The mechanisms that regulate their characteristic properties and prepare them for their encounter are poorly understood. However, when motor axons reach their target muscles the interaction between these cells profoundly affects their survival and further development. The earliest interactions between motoneurones and muscle fibres generate a form of activity which is in many ways different from that seen at later stages. This difference may be due to the immature types of ion channels and neurotransmitter receptors present in the membranes of both motoneurones and muscle fibres. For example, spontaneous release of acetylcholine may influence the myotube even before any synaptic specialization appears. This initial form of activity-dependent interaction does not necessarily depend on the generation of action potentials in either the motoneurone or the muscle fibre. Nevertheless, the ionic fluxes and electric fields produced by such interactions are likely to activate second messenger systems and influence the cells. An important step for the development of the motor unit in its final form is the initial distribution of synaptic contacts to primary and secondary myotubes and their later reorganization. Mechanisms that determine these events are proposed. It is argued that the initial layout of the motor unit territory depends on the matching of immature muscle fibres (possibly secondary myotubes) to terminals with relatively weak synaptic strength. Such matching can be the consequence of the properties of the muscle fibre at a particular stage of maturation which will accept only nerve terminals that match their developmental stage. Refinements of the motor unit territory follows later. It is achieved by activity-dependent elimination of nerve terminals from endplates that are innervated by more than one motoneurone. In this way the territory of the motor unit is established, but not necessarily the homogeneity of the physiological and biochemical properties of its muscle fibres. These properties develop gradually, largely as a consequence of the activity pattern that is imposed upon the muscle fibres supplied by a given motoneurone. This occurs when the motor system in the CNS completes its development so that specialized activity patterns are transmitted by particular motoneurones to the muscle fibres they supply.(ABSTRACT TRUNCATED AT 400 WORDS)