RESEPTOR Kanal Ion (IONOTROPIK RESEPTOR)

1. RESEPTORKanal Ion(IONOTROPIK RESEPTOR)

2. The Nervous System Neurons: cell body, dendrite, axon Glucose: ~100 g/day Ionic gradients across membrane Blood-brain barrier: water soluble molecules by transporters glucose, O2 etc A motor nerve cell and investing membranes

3. Ligand-Gated Ion Channel Receptors Nerve-nerve or nerve-muscle synapsis Very rapid (msec) with minimal enzymatic steps Neurotransmitters (amino acid derivatives etc) released from vesicles. Low affinity (mM-mMKd): rapid association/dissociation Neurotransmitter-gated ion channel receptors

7. Neurotransmitters Excitatory neurotransmitters (depolarizing) Acetylcholine Aspartate Dopamine Histamine Epinephrine Glutamate Inhibitory neurotransmitters (Hyperpolarizing) 4-Aminobytyrate (GABA) Glycine Taurine

12. PDH complex (FAD, lipoamide, TPP) Pyruvate Reuptake or diet Acetylcholine Acetate + choline Acetylcholine Synthesis and Degradation Acetyl-CoA + choline Choline acetyltransferase (CAT) (inhibited by mercurials) Acetylcholinesterase (AChE) (membrane associated; inhibited by nerve agents, sarin)

13. Acetylcholine neurotransmission Acetylcholine synthesized from choline and acetyl CoA by choline acetyltransferase (ChAT) ACh loaded into synaptic vesicles by VAchT Released ACh broken down by acetylcholinesterase (notable difference from other neuro-transmitters discussed so far) Choline taken up by presynaptic terminal as precursor to further ACh synthesis

14. Antagonis Reseptor Nikotinik • Letak reseptor: ganglia otonom, NMJ • Contoh obat pemblok ganglion : heksametonium, trimetafan  tidak digunakan lagi karena efek pada aksi simpatik dan parasimpatik  ESO besar • Obat pada NMJ : non-depolarizing blocking agent dan depolarizing blocking agent

22. Agonis Reseptor Nikotinik • Contoh senyawa/obat : Nikotin, Lobelin • Nikotin : berikatan dengan Reseptor asetilkolin nikotinik di SSP  peningkatan kewaspadaan, euforia ringan, mual dll • Obat untuk membantu mengatasi gejala putus rokok : Vareniklin

25. The chief inhibitory neurotransmitter in the mammalian central nervous system • Neurons that produce GABA as their output are called GABAergic neurons GABA-γ-Aminobutyric acid

26. GABAA–aligand-gated ion channel

27. Composed of two subunits • When binding to the GABAB receptor activates the trimeric G protein • Inhibit voltage-gated Ca++ channels or activate K+ channels. GABAB-a G protein-coupled receptor

28. synthesis

29. GABA receptors: Fast GABA transmission mediated mainly by GABAA receptors, which are ligand-activated chloride channels. Some fast GABA transmission mediated by so-called GABAC receptors, which are a closely-related sub-family of GABAA receptors GABA also utilizes a metabotropic receptor called the GABAB receptor, described in Neuromodulation section.

35. GABAA receptor pharmacology Antagonists: Bicucculine competitive SR95531 (gabazine) competitive Picrotoxin mixed competitive, non-competitive Penicillin G open channel block Pentelenetetrazole (PTZ) open channel block Pregnenolone sulfate non-competitive Agonist: Muscimol Barbiturates, neurosteroids (high concentrations) Enhancers: Benzodiazepines Barbiturates, neurosteroids (low concentrations) GABAA receptor antagonists are important research tools, but not clinically useful. GABAA receptor enhancement, but not direct agonism, is useful therapeutically in neurology.

36. Glutamat Receptor

37. glutamate receptor (GluR) is the most important excitatory transmitter in the CNS

38. Ionotropic Glutamate Receptors AMPA KA NMDA

41. StructureIonotropic Glutamate Receptors AMPA-R NMDA-R

42. NMDA receptors

49. 5-Hydroxytryptamine (Serotonin) Derived from tryptophan Terminated by reuptake Serotonin deficiency: depression Paxil, Prozac, Zoloft: antidepressants Degradation of serotonin