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Chapter: Biochemical Pharmacology : Drugs that act on sodium and potassium channels

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Structure and function of synapses

As we have seen, the presynaptic action potential will open voltage-gated calcium channels and thereby trigger exocytosis of the neurotransmitter that is stored in vesicles.

Structure and function of synapses

As we have seen, the presynaptic action potential will open voltage-gated calcium channels and thereby trigger exocytosis of the neurotransmitter that is stored in vesicles. The transmitter will then bind to a postsynaptic receptor. This will typically result in a local change to the postsynaptic membrane potential, which may or may not trigger a com-plete action potential (Figure 7.3). While a great many dif-ferent transmitters exist, individual neurons only seem to be using very few different ones. Although the time-honoured textbook dogma of one transmitter per neuron only is no longer valid, we will, for the purpose of this class, pretend it to be.

 

Calcium promotes transmitter exocytosis at multiple stages. There are several pools of neurotransmitter vesicles in the nerve ending, which differ by their maturity (e.g., amount of transmitter stored) and their availability for immediate exocytosis. One effect of calcium consists in the recruitment of vesicles from an immobile, cell skeleton-attached pool into the mobile pool. This is achieved by calmodulin-dependent phosphorylation of synapsin, a protein associat-ed with the cytosolic surface of the vesicle membrane. Mo-bilized vesicles will attach themselves to the cytoplasmic membrane. Attachment is mediated by mutual recognition of so-called SNARE membrane proteins located on both the vesicle and the cytoplasmic membrane. One such pro tein - synaptobrevin - is the target of tetanus and botulinum toxins.

The very fast release of neurotransmitter (1 millisecond after presynaptic excitation) is due to the exocytosis from pre-attached vesicles. This is effected via synaptotagmin, which binds and directly responds to calcium. Besides the proteins mentioned, there is a somewhat distressing multi-tude of additional proteins also participating in neurotrans mitter release. The precise roles of most of these proteins remain unsettled.


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