KINETICS, CA2-MEDIATED MECHANICAL MODULATION OF TRANSMITTER RELEASE FROM FROG MOTOR-NERVE TERMINALS( DEPENDENCE, AND BIOPHYSICAL PROPERTIESOF INTEGRIN)

Neurotransmitter release from frog motor nerve terminals is strongly m odulated by change in muscle length. Over the physiological range, the re is an similar to 10% increase in spontaneous and evoked release per 1% muscle stretch. Because many muscle fibers do not receive suprathr eshold synaptic inputs at rest length, this stretch-induced enhancemen t of release constitutes a strong peripheral amplifier of the spinal s tretch reflex. The stretch modulation of release is inhibited by pepti des that block integrin binding of natural ligands. The modulation var ies linearly with length, with a delay of no more than similar to 1-2 msec and is maintained constant at the new length. Moreover, the stret ch modulation persists in a zero Ca2+ Ringer and, hence, is not depend ent on Ca2+ influx through stretch activated channels. Eliminating tra nsmembrane Ca2+ gradients and buffering intraterminal Ca2+ to approxim ately normal resting levels does not eliminate the modulation, suggest ing that it is not the result of release of Ca2+ from internal stores. Finally, changes in temperature have no detectable effect on the kine tics of stretch-induced changes in endplate potential (EPP) amplitude or miniature EPP (mEPP) frequency. We conclude, therefore, that stretc h does not act via second messenger pathways or a chemical modificatio n of molecules involved in the release pathway. Instead, there is dire ct mechanical modulation of release. We postulate that tension on inte grins in the presynaptic membrane is transduced mechanically into chan ges in the position or conformation of one or more molecules involved in neurotransmitter release, altering sensitivity to Ca2+ or the equil ibrium for a critical reaction leading to vesicle fusion.