The Journal of General Physiology, Vol 100, 881-901, Copyright © 1992 by The Rockefeller University Press
Nature of increase in quantal release by the thallous ion at frog end plates with and without nerve stimulation
PA Talbot
Department of Pharmacology, Meharry Medical College, Nashville, Tennessee 37208.
The monovalent thallous ion (Tl) was evaluated at the frog end plate in
vitro with intracellular microelectrodes. Recordings included end plate
potentials (EPPs), and miniature end plate potentials (MEPPs). Replacement
of extracellular potassium (K) by 2.5 mM Tl (a) caused increases in MEPP
and EPP amplitudes, MEPP frequency, and quantal content, and (b) caused
complete recovery of the EPP facilitation index at BAPTA-loaded nerve
terminals. Tl's effects were reversible and concentration dependent, and
persisted for > 3 h. The increase in MEPP frequency and its rate of
decline due to Tl washout were more pronounced at 0 calcium (Ca)-2 mM EGTA
than at 0.3 mM EGTA, suggesting that Tl's effects were not due to elevation
of internal Ca. Unlike heavy metal ions reportedly capable of substituting
for Ca, 0.2 mM Tl did not block, but further enhanced, elevated MEPP
frequencies, occurring after nerve stimulation or in high K, to greater
levels with barium (Ba) than with Ca. 200 nM omega-conotoxin (omega-CTX)
blocked Tl's effect, indicating that Tl primarily entered the nerve
terminal via Ca channels. A 50% reduction in sodium (Na) did not modify
Tl's effect, although removal of K in the presence of 20 microM ouabain and
2.5 mM Tl caused an exaggerated increase in MEPP frequency, which decreased
with a 50% reduction in Na. Based on the analysis, Tl neither substituted
for Ca nor elevated internal Ca and Na, nor were its effects antagonized by
ouabain; Tl increased quantal secretion, possibly by a fusogenic mechanism,
after its entry into the nerve terminal.
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