Title: On nerve pulse transmission in cholinergic synapses
Abstract: Presently, it is assumed that nerve pulse transmission in
cholinergic synapses takes place as follows: Acetylcholine (ACh) (i) is
released by a nerve cell, (ii) binds to receptor proteins on a
neighbouring cell (e.g. muscle, nerve, gland, etc.) and (iii) is
subsequently degraded via acetylcholinesterase (AChE).
This model contains a central, yet rarely mentioned, deficiency: Esterase
is ubiquitously present in the synaptic cleft and it is one of the fastest
catalysts in nature (turnover number: around 10000 molecules per second).
Accordingly, any ACh liberated into the synapse will be hydrolzyed at a
remarkable rate. Thus, it is not ACh that acts on the postsynaptic
membrane, but a mixture containing ACh, acetic acid and choline. If one
claims, as is usually done, that AChE cleans up the synapse, one needs
unambiguous evidence that choline and acetic acid are without excitatory
effect. Such experiments have been lacking.
Herein, we studied the effects of ACh and its hydrolysis products on
excitable cells (Chara australis internodes). These cells are unresponsive
to ACh. However, they were rendered ACh-sensitive in the presence of AChE.
This was underlined by a clear difference in cell membrane depolarisation
upon exposure to intact ACh (∆V=-2±5 mV average±StDev (n=6)) and its
hydrolysate respectively (∆V=81±19 mV (n=14)). Depolarisation, which
triggered action potentials, was attributed to one of the hydrolysis
products: acetic acid/protons (∆V=87±9 mV at pH 4 (n=5); choline
ineffective [1-10 mM] (n=3)).
Our results indicate that transmission of a pulse from one cell to another
can be achieved by release of ACh in the presence of AChE. This was first
proposed by Konrad Kaufmann in the 1970s. It is not necessary to postulate
an ACh-binding protein ("receptor"). Protons liberated during hydrolysis
of ACh excite the negatively charged cell membrane. AChE, in contrast to
the presently predominant conception, does not ?deactivate? ACh but rather
releases excitatory protons.