The Drosophila and Manducahearts as models for studying the role of innervation in cardiac function
AdvisorLevine, Richard B.
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PublisherThe University of Arizona.
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AbstractCardiac activity of Drosophila melanogaster and Manduca sexta changes during metamorphosis. The larval heart has only anterograde contractions. Adult heart activity becomes a cyclic alternation of anterograde and retrograde contractions originated by putative anterograde and retrograde pacemakers. During development, the larval skeletal muscle motoneuron-1 in abdominal segments 7 and 8 becomes respecified to innervate the terminal cardiac chamber of adult Manduca and undergoes morphological and physiological reorganization. MNs-1 activate and sustain the anterograde pacemaker activity of the terminal chamber. The innervation of the adult abdominal heart of Drosophila melanogaster was studied to determine whether the adult heart receives neuronal input or whether its complex activity must be considered independent from the nervous system. The larval heart lacks innervation suggesting a myogenic cardiac impulse. At metamorphosis, neural processes grow onto the myocardium. A pair of glutamatergic transverse nerves innervates bilaterally each cardiac chamber. In addition, CCAP-immunoreactive fibers originating from peripheral, bipolar neurons (BpNs) fasciculate with the transverse nerve projections and terminate segmentally throughout the abdominal heart. To determine the role of this innervation in cardiac function, a novel optical technique based on the movement of GFP-labeled nerve terminals was developed to monitor heartbeat in intact preparations. Simultaneous monitoring of adjacent cardiac chambers revealed the direction of contractions and allowed correlation with volume changes. Intracellular recordings from the first abdominal cardiac chamber, the conical chamber, revealed pacemaker action potentials and the excitatory effect of local glutamate application. Bath-applied glutamate initiated retrograde contractions in semi-intact preparations. Similarly, electrical stimulation of the transverse nerve that serves the conical chamber caused a chronotropic effect and initiation of retrograde contractions. This effect is distinct from that of peripheral CCAP-immunoreactive neurons, which potentiate the anterograde beat. Cardiac reversal was evoked pharmacologically by sequentially applying CCAP and glutamate to the heart. The role of the neuropeptide, Crustacean Cardioactive Peptide (CCAP) in adult Drosophila melanogaster cardiac function was studied by RNA interference (RNAi) and targeted cell ablation. CCAP has a cardioacceleratory effect when it is applied in vitro. Lack of CCAP-innervation in CCAP knock-out flies altered one cardiac phase, the anterograde beat, without preventing the cyclic cardiac reversal.
Degree ProgramGraduate College