Basic neurophysiology 3

Basic neurophysiology 3

1. DALE'S PRINCIPAL-a neuron only releases one transmitter type, however often both synaptic & secretory vesicles

   • Ach=cholinergic/NA-noradrenergic/Glu=glutamatergic/GABA-GABAergic (all synaptic), Peptides=peptidergic (secretory)
     • Peptides are neuromodulators which modulate the effect of neurotransmitters
     • Glutamatergic neurons-glutamate primary neurotransmitter (main excitatory neurotransmitter of mammalian CNS)
       • Metabotrophic glutamate receptor
       • Ionotropic (ligand-gated channels); AMPAr, NMDAr,KAINATEr (named after the neuromodulators they bind)
     • GABAergic (inhibitory) neurons
       • GABA & glycine-ligand-gated receptor/channels. Synaptic inhibition mediated by GABA in CNS, Glycine in PNS
         • Both transmitters regulate cloride channels=HYPERPOLARISATION
           • synaptic inhibition is very tightly regulated-too much=loss of consciousness & coma, too little=seizures
       • psychotropic drugs can act on GABA receptor. Most modulatory (GABA must be bound)
         • They increase open probability so more permeability to Cl-=Cl- influx=outward current Icl=hyperpolarisation=increased inhibition (IPSP)=slow down
       • Hyperplexia/'startle disease'=stiffness in babies,lifelong exaggerated startle response (scared stiff)
         • Genetic disease-mutations in glycine receptor, glycine inhibitory neurotransmitter in the PNS=reduced inhibitory responses

2. Catecholaminergic-Catcholamine=tyrosine precursor common to DA,NA & A.Transmitters have no breakdown enzyme so re-uptake critical to turn off signal

   • Cocaine-targets DA re-uptake transporter
   • Amphetamines-target DA & NA reuptake systems
   • catecholaminergic neurons-involved in reg of movement, mood, attention & visceral function
     • movement disorder-parkinsons-dopaminergic neurons slowly die
       • DaTSCAN-radiolabelled cocaine analogue-targets DA re-upatake transporter in dopaminergic neurons=less & weaker signal in parkinsons patients
       • L-DOPA-precursor of DA-allows more DA to synthesise-temp measure because neurons continue to die