Hypertonic enhancement of transmitter release from frog motor nerve terminals: Ca2+ independence and role of integrins.
Hyperosmotic solutions cause markedly enhanced spontaneous quantal release of neurotransmitter from many nerve terminals. The mechanism of this enhancement is unknown. We have investigated this phenomenon at the frog neuromuscular junction with the aim of determining the degree to which it resembles the modulation of release by stretch, which has been shown to be mediated by mechanical tension on integrins. The hypertonicity enhancement, like the stretch effect, does not require Ca2+ influx or release from internal stores, although internal release may contribute to the effect. The hypertonicity effect is sharply reduced (but not eliminated) by peptides containing the RGD sequence, which compete with native ligands for integrin bonds. There is co-variance in the magnitude of the stretch and osmotic effects; that is, individual terminals exhibiting a large stretch effect also show strong enhancement by hypertonicity, and vice versa. The stretch and osmotic enhancements also can partially occlude each other. There remain some clear-cut differences between osmotic and stretch forms of modulation: the larger range of enhancement by hypertonic solutions, the relative lack of effect of osmolarity on evoked release, and the reported higher temperature sensitivity of osmotic enhancement. Nevertheless, our data strongly implicate integrins in a significant fraction of the osmotic enhancement, possibly acting via the same mechanism as stretch modulation.
Kashani
A H
AH
Department of Physiology, Jerry Lewis Neuromuscular Research Center, UCLA School of Medicine, University of California, Los Angeles, CA 90095, USA.
Chen
B M
BM
Grinnell
A D
AD
D000818:Animals; D002118:Calcium / Q000502:physiology; D005260:Female; D006982:Hypertonic Solutions / Q000494:pharmacology*; D016023:Integrins / Q000502:physiology; D007700:Kinetics; D008297:Male; D009046:Motor Neurons / Q000378:metabolism*; D009411:Nerve Endings / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009994:Osmolar Concentration; D011894:Rana pipiens; D013314:Stress, Mechanical
D006982:Hypertonic Solutions; D016023:Integrins; D018377:Neurotransmitter Agents; D002118:Calcium