Zellautonome, homöostatische Regulation der elektrischen Erregbarkeit von Körperwandmuskelzellen der Taufliege Drosophila melanogaster

It is essential for excitable cells to keep their activity within a physiological and appropriate range independently from changes in synaptic efficacy or cellular excitability which can occur during phases of learning and/or development. Recently shown results indicated that excitable cells like neurons and muscles are capable of regulating their own activity. Most of those studies, however showed compensatory effects at the level of synaptic efficacy. Those showing changes in ion channel expression to maintain cellular excitability are rare and therefore less understood. Using the advantages of the Drosophila Gal4/UAS-System I generated muscle-specific mutant larvae that expressed a modified Shaker-potassium channel leading to a dramatically decreased cellular excitability. The aim of this work was to detect possible compensatory changes at the level of ion channels and study the underlying cellular mechanisms. Measurements of muscle performance did not display severe impairments in the contractile properties (tension and kinetics) when mutants were compared with wildtypes thus suggesting some kind of compensatory changes. Additional experiments excluded changes of motor synaptic transmission and/or motoneuronal output. On the level of ion channels, an increased calcium current amplitude of about 30% was detected in mutant muscle cells, which was accompanied by an up-regulation of the corresponding calcium channel beta-subunit expression rate. Finally a different mutant was tested, which expressed the Shaker gene late in development and thus had only a limited time for possible compensation. In contrast to the "early" shaker-mutant, this "late" mutant showed impaired muscle performance. This experiment suggested that the expression of the genetically modified potassium channel leads to severe impairments of contractile properties if the effect had no time to be compensated by an increased calcium current