Transmitter release at mouse motor nerve terminals mediated by temporary accumulation of intracellular barium.
1. In isolated mouse diaphragm, tetanic nerve stimulation in the presence of Ba2+ causes an increase in frequency of MEPPs which continues as an after-discharge or 'tail' of raised MEPP frequency that subsides over a period of seconds, in addition to EPPs of low quantal content. 'Ba2+ tails' are also seen with focal depolarization of nerve terminals in the presence of tetrodotoxin. 2. The development of 'Ba2+ tails' could be inhibited or blocked by neomycin, raised Mg2+, or Cd2+ present at the time of stimulation; the presence of the blocking substance during the tail itself had no effect. 3. The time course of MEPP frequency changes during and after stimulation could be expressed as a simple exponential process, with the same time constant for both the rise and the fall, by taking as the time-dependent variable the nth root of MEPP frequency, n being 4 or 5. The time constant (tau) derived from the rate of fall of the 1/4 power of MEPP frequency during the tail was at most junctions between 3 and 6 s, and apparently unaffected by concentration of Ba2+, or of Ca2+, or by tonic depolarization of the nerve terminal. 4. The intensity of 'Ca2+ tails' was graded steeply with the number of stimuli applied, but was nearly independent of stimulus frequency, when train duration was kept brief compared to tau, i.e. about a second or less. The nth root of the number of MEPPs at a given time period in the tail was linearly related to the number of stimuli, when n was chosen to be 4 or 5. 5. The above data are consistent with a model in which (a) with each nerve impulse in a train there occurs the same entry of Ba2+ into the terminal, (b) transmitter release (MEPP frequency) is proportional to the fourth or fifth power of [Ba2+] at critical sites within the nerve terminal, (c) the Ba2+ leaves these sites as a first-order process with a time constant of a few seconds. Compared to Ca2+, Ba2+ persists longer but has lower potency. 6. With variation of external [Ba2+] over the range 50 microM to 6.4 mM, apparent Ba2+ entry per nerve impulse grew linearly with concentration. 7. Evidence is presented indicating that intraterminal Ba2+ can 'co-operate' with Ca2+ or La3+ in promoting transmitter release.
Quastel
D M
DM
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
Saint
D A
DA
D015761:4-Aminopyridine; D000200:Action Potentials / Q000187:drug effects; D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000502:physiology*; D004533:Egtazic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology; D051379:Mice; D009045:Motor Endplate / Q000502:physiology*; D009132:Muscles / Q000502:physiology*; D009355:Neomycin / Q000494:pharmacology; D009469:Neuromuscular Junction / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D011898:Ranidae; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors
D000631:Aminopyridines; D018377:Neurotransmitter Agents; D001464:Barium; D013779:Tetrodotoxin; D004533:Egtazic Acid; D015761:4-Aminopyridine; D009355:Neomycin; D008274:Magnesium