Calmodulin increases transmitter release by mobilizing quanta at the frog motor nerve terminal.
The role of calmodulin (CaM) in transmitter release was investigated using liposomes to deliver CaM and monoclonal antibodies against CaM (antiCaM) directly into the frog motor nerve terminal. Miniature endplate potentials (MEPPs) were recorded in a high K+ solution, and effects on transmitter release were monitored using estimates of the quantal release parameters m (number of quanta released), n (number of functional transmitter release sites), p (mean probability of release), and var(s) p (spatial variance in p). Administration of CaM, but not heat-inactivated CaM, encapsulated in liposomes (1000 units ml(-1)) produced an increase in m (25%) that was due to an increase in n. MEPP amplitude was not altered by CaM. Administration of antiCaM, but not heat-inactivated antiCaM, in liposomes (50 microl ml(-1)) produced a progressive decrease in m (40%) that was associated with decreases in n and p. MEPP amplitude was decreased (15%) after a 25 min lag time, suggesting a separation in time between the decreases in quantal release and quantal size. Bath application of the membrane-permeable CaM antagonist W7 (28 microM) produced a gradual decrease in m (25%) that was associated with a decrease in n. W7 also produced a decrease in MEPP amplitude that paralleled the decrease in m. The decreases in MEPP size and m produced by W7 were both reversed by addition of CaM. Our results suggest that CaM increases transmitter release by mobilizing synaptic vesicles at the frog motor nerve terminal.
Brailoiu
Eugen
E
Department of Pharmacology, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, TN 37614-1708, USA.
Miyamoto
Michael D
MD
Dun
Nae J
NJ
D000818:Animals; D002147:Calmodulin / Q000494:pharmacology*; D066298:In Vitro Techniques; D009045:Motor Endplate / Q000187:drug effects* / Q000378:metabolism; D009489:Neurosecretion / Q000187:drug effects / Q000502:physiology; D018377:Neurotransmitter Agents / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000378:metabolism; D011894:Rana pipiens; D013572:Synaptic Vesicles / Q000187:drug effects* / Q000378:metabolism
D002147:Calmodulin; D018377:Neurotransmitter Agents