Journal of Neuroscience, Vol 6, 681-690, Copyright © 1986 by Society for Neuroscience
Excitatory action of ATP on embryonic chick muscle
RI Hume and MG Honig
It has been suggested that ATP might play a role in synaptic transmission
at developing vertebrate neuromuscular junctions. To increase our
understanding of the events underlying synapse formation, we have used
intracellular recording and patch clamp recording to examine the response
of chick myoblasts and myotubes to to ATP and other nucleotides, ATP,
applied at micromolar concentrations, has a potent depolarizing action on
chick myoblasts and myotubes. The ATP depolarization declines during
prolonged application of ATP and shows no recovery for at least 20 min
after the removal of ATP. The physiological event that underlies the ATP
response has a reversal potential near O mV and is due to a conductance
increase. However, contrary to our expectation, in a series of nearly 200
cell-attached and outside-out patch recordings, we did not detect
single-channel currents that were related to ATP. The myotube ATP receptor
is pharmacologically distinct from putative ATP receptors in other systems.
It is not activated by ADP, AMP, or adenosine. Furthermore, the
nonhydrolyzable ATP analogs, AMP-PNP, alpha,beta-meATP, and
beta,gamma-meATP (respectively, 5-adenylylimido diphosphate; alpha,beta-
methylene adenosine 5'-triphosphate; and beta,gamma-methylene adenosine
5'-triphosphate), which are potent ATP agonists in other systems, have no
depolarizing action on myotubes. The ATP receptor is also distinct from the
nicotinic ACh receptor since responses to ATP are unaffected by the
nicotinic antagonists d-tubocurarine and alpha-bungarotoxin. We therefore
applied alpha-bungarotoxin to nerve-muscle co-cultures in the hope of
uncovering an additional component of the postsynaptic potential, which
might represent a synaptic action of ATP. Under these experimental
conditions no evidence indicative of a postsynaptic action of ATP released
from nerve terminals was observed.
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