1. Neurotransmitter Types Scanned from Squires et. al. Fundamental Neuroscience

2. Patton’s Requirements for Neurotransmitters 1 Neurotransmitters must be synthesized in the presynaptic neuron: in the cell body and transmitted to the terminal end button or synthesized within the terminal end button.

3. 2 The substance should be released from the nerve terminals in a chemically- pharmacologically identifiable form.

5. 3 A neurotransmitter should reproduce at the postsynaptic cell the specific events (such as changes in membrane properties) that are seen after stimulation of the presynaptic neuron.

6. 4 (A) The effects of a putative neurotransmitter should be blocked by competitive antagonists of the receptor for the transmitter in a dose dependent manner. (B) Treatments that inhibit synthesis of the transmitter should block the effects of presynaptic stimulation

7. 5. There should be active mechanisms to terminate the action of the putative neurotransmitter (uptake by the presynaptic neuron or glial cells through specific transport mechanisms, or enzymatic inactivation of the chemical messenger).

9. Two Large Categories of Neurotransmitters Traditional Nontraditional

13. GABA synapse

14. Nontraditional synapses Peptide synapses Nitric oxide (the gas)

15. Peptide synapse

16. Nitric Oxide

17. Ionotrophic synapses nACh receptor is opened by ACH, such that all small ions (Na+, K+, Cl-) run down their diffusion gradiant.

18. Metatrophic Neurotransmitter opens gates if coupled with G proteins.

19. Acetylcholine neuromuscular Junction At the end of the 1930s and early 40s the general conclusion was reached that the first post synaptic event was a negative going depolarization of the muscle fiber. Named the end-plate potential Was restricted to the end-plate region. Is sufficient in size to generate and action- potential which propagates the length of the fiber.

20. Acetylcholine Dale investigated a substance obtained from ergot a fungal infection of cereal. Slowed heart rate of the cat, and lowered blood pressure. Hypothesized that acetylcholine occurred naturally in the body and hydrolized by an enzyme in the body accounting for the inpossabillity of it being isolate in from the body.

21. Lowe’s study on frog heart Found that stimulation of the Vagus nerve caused heart1 to lengthen the beat to beat time frame slowing heart rate. An aliquot of the perfusion fluid of heart1 when transfered to heart 2, with no stimulation of heart2’s Vagus nerve caused heart 2 lengthen its beat to beat time frame and slow heart 2 down.

22. Dale and Dudley’s study Isolated acetylcholine from the spleen of cows and horses. Demonstration that acetylcholine could be isolated from the ganglia of the sympathetic nervous system and at nerve terminals in the motor muscles of the sckelatal. system

23. Construction-Destruction Construction Acetyl Co A + choline == Acetylcholine Destruction Acetylcholine + acetylcholinesterase == choline + acetic acid

24. Drawing the neural endplate and underlying muscle

25. Legend for previous slide

26. Fatt and Katz study Arrangement for Intracellular recording of post synaptic neuromuscular junction

27. Using the apparatus from the previous slide for Intracellular recording of post synaptic neuromuscular junction. The electrode is rode is progressively move away from the axon in mm steps

28. Voltage clamp

29. Results of voltage clamp study

30. Electrical stimulation of the axon of the presynaptic membrane is different in from direct stimulation of the muscle fiber.

31. Iontophertic injections of Ach, developed by Nastuk (1953) further developed by Katz and del Catillo (1955)

32. del Castillo and Katz study results

33. Miniature end-plate potentials In the resting membrane, small potentials of about 0.5mV can be recorded. Could only be found at the end-plate in curarized preparations. Could not be found in preparations where the muscle had been previously denervated two weeks previously.

34. Miniature end-plate potentials

35. Characteristics of the miniature end-plate potential According to Katz, the frequency of the miniature end-plate potentials is controlled by the conditions of the presynaptic membrane, while the amplitude is controlled by the properties of the postsynaptic membrane

36. Quantal release of Acetylcholine A combination of Mg and Ca can be used to block the release of ACH. When this concentration if used appropriately, the size of the successive EPP will fluctuate in a step-wize manner (see curve below).