  One of the most conserved mechanisms for transmission of a nerve pulse across
a synapse relies on acetylcholine. Ever since the Nobel-prize winning works of
Dale and Loewi, it has been assumed that acetylcholine - subsequent to its
action on a postsynaptic cell - is split into inactive by-products by
acetylcholinesterase. Herein, this widespread assumption is falsified.
Excitable cells (Chara australis internodes), which had previously been
unresponsive to acetylcholine, became acetylcholine-sensitive in presence of
acetylcholinesterase. The latter was evidenced by a striking difference in cell
membrane depolarisation upon exposure to 10 mM intact acetylcholine
(deltaV=-2plus/minus5 mV) and its hydrolysate respectively
(deltaV=81plus/minus19 mV) for 60 sec. This pronounced depolarization, which
also triggered action potentials, was clearly attributed to one of the
hydrolysis products: acetic acid (deltaV=87plus/minus9 mV at pH 4.0; choline
ineffective in range 1-10 mM). In agreement with our findings, numerous studies
in the literature have reported that acids excite gels, lipid membranes, plant
cells, erythrocytes as well as neurons. Whether excitation of the postsynaptic
cell in a cholinergic synapse is due to protons or due to intact acetylcholine
is a most fundamental question that has not been addressed so far.
