Homeostatic control of presynaptic release is triggered by postsynaptic membrane depolarization

Homeostatic mechanisms regulate synaptic function to maintain nerve and mus cle excitation within reasonable physiological limits. The mechanisms that initiate homeostasic changes to synaptic function are not known. We specifi cally impaired cellular depolarization by expressing the Kir2.1 potassium c hannel in Drosophila muscle. In Kir2.1-expressing muscle there is a persist ent outward potassium current (similar to 10 nA), decreased muscle input re sistance (50-fold), and a hyperpolarized resting potential. Despite impaire d 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), com pensates for altered muscle excitation. Because morphological synaptic grow th is normal, we conclude that a homeostatic increase in presynaptic releas e compensates for impaired muscle excitability. These data demonstrate that a monitor of muscle membrane depolarization is sufficient to initiate syna ptic homeostatic compensation.