Selective effect of cell membrane on synaptic neurotransmission

Neurotransmission regulates a variety of senses and functions such as motivation, memory and muscle contraction. Neurotransmitters (NTs) play a key role in these functions since the signal transmission takes place through the binding of a NT with its specific receptor embedded in the postsynaptic membrane. Understanding the details of NT binding is important given that various diseases emerge if the signaling is impaired.

Atomistic molecular dynamics simulations were performed with 13 non-peptidic neurotransmitters (NTs) in three different membrane environments. The results provide compelling evidence that NTs are divided into membrane-binding and membrane-nonbinding molecules. NTs adhere to the postsynaptic membrane surface whenever the ligand-binding sites of their synaptic receptors are buried in the lipid bilayer. In contrast, NTs that have extracellular ligand-binding sites do not have a similar tendency to adhere to the membrane surface. This finding is a seemingly simple yet important addition to the paradigm of neurotransmission, essentially dividing it into membrane-independent and membrane-dependent mechanisms. Moreover, the simulations also indicate that the lipid composition especially in terms of charged lipids can affect the membrane partitioning of NTs. The revised paradigm, highlighting the importance of cell membrane and specific lipids for neurotransmission, should to be of interest to neuroscientists, drug industry and the general public alike.

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