Homeostatic control of presynaptic release is triggered by postsynaptic membrane depolarization.
Homeostatic mechanisms regulate synaptic function to maintain nerve and muscle excitation within reasonable physiological limits. The mechanisms that initiate homeostasic changes to synaptic function are not known. We specifically impaired cellular depolarization by expressing the Kir2.1 potassium channel in Drosophila muscle. In Kir2.1-expressing muscle there is a persistent outward potassium current ( approximately 10 nA), decreased muscle input resistance (50-fold), and a hyperpolarized resting potential. Despite impaired muscle excitability, synaptic depolarization of muscle achieves wild-type levels. A quantal analysis demonstrates that increased presynaptic release (quantal content), without a change in quantal size (mEPSC amplitude), compensates for altered muscle excitation. Because morphological synaptic growth is normal, we conclude that a homeostatic increase in presynaptic release compensates for impaired muscle excitability. These data demonstrate that a monitor of muscle membrane depolarization is sufficient to initiate synaptic homeostatic compensation.
Paradis
S
S
Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94143, USA.
Sweeney
S T
ST
Davis
G W
GW
D000818:Animals; D004330:Drosophila; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology*; D015870:Gene Expression / Q000502:physiology; D006706:Homeostasis / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology; D009046:Motor Neurons / Q000502:physiology; D009132:Muscles / Q000294:innervation / Q000502:physiology; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying; D017729:Presynaptic Terminals / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology*
D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D017470:Receptors, Glutamate; D011188:Potassium