Friday, October 7^th

structure of the synapse
-importance of Ca++--without calcium entry through voltage-gated calcium channels, the action potential could not stimulate neurotransmitter release.
-opening/closing channels in postsynaptic membrane-
-leads to small depolarizations or HYPERPOLARIZATIONS-increases in the charge difference between the inside of the outside (entry of Cl-; exit of K+). These small changes in membrane potential are summed at cell body/axon hillock…if a suprathreshold depolarization is reached, there will be an action potential in the post-synaptic neuron. Hyperpolarizations are inhibitory events…make the post-synaptic neuron less likely to fire an action potential (bring it further away from threshold).

Excitatory or Inhibitory neurotransmitters-

Whether an excitatory or inhibitory effect DEPENDS ENTIRELY ON THE TYPE OF ION CHANNEL!! (although some NT’s exclusive cause depolarizations and hyperpolarizations because its receptors are always linked to a particular type of channel).

Review steps of neurotransmission we've learned thus far, and discuss how drugs can affect neural transmission.

Drugs can cause psychoactive (mind altering) effects if they get through the blood brain barrier (most psychoactive drugs are small or lipid soluble, two factors that allow molecules to pass through the BBB), and alter neurotransmission. Drugs can either be agonists (increase or mimic the effects of neurotransmitter) or antagonists (decrease or block the effects of the neurotransmitter)

Steps in neurotransmission:

1. Neurotransmitter synthesized (in cell body, from enzymatic action that converts amino acids into NT’s). l-dopa is an agonist at this stage…it is a precursor to dopamine (the synthetic pathway for DA: tyrosineàl-dopaàdopamine) that crosses the BBB…it can be administered to Parkinson’s patients who have lost DA due to degeneration of brain area that produces DA…the remaning cells take up l-dopa and produce DA in higher concentrations than would otherwise be produced. Thus, it is an agonist.

2. Neurotransmitter transported and stored in axon terminal. Reserpine is an antagonist at this stage, because it pokes holes in synaptic vesicles, making them leak neurotransmitter prior to release. Thus, when the vesicles migrate, there is less neurotransmitter to be released.

3. Action potentials travels down pre-synaptic axon, depolarizing current arrives at the axon terminal, causes Ca++ entry; vesicles migrate, fuse with presynaptic membrane, contents spill into cleft. Amphetamine is an agonist at this stage—it causes more vesicles to migrate and release neurotransmitter for each action potential.

4. NT binds to postsynaptic membrane, initiates depolarizing/hyperpolarizing event. Morphine is an agonist at this stage—it binds to postsynaptic receptors, mimicking the endogenous opioid neurotransmitters—it is similar in structure to these NT’s and “fools” the postsynaptic neuron into thinking there’s been NT released. Naloxone, on the other hand, is an antagonist at this stage. It binds to postsynaptic receptor but DOES not open the affiliated channel.

5. NT is removed from the synapse (through either enzymatic degradation or reuptake via transporter molecules). Monoamine oxidase inhibitors block the breakdown of NT’s..thus they are AGONISTS (they prevent the removal of NT’s from the synapse). Cocaine is an agonist because it blocks the reuptake (removal) of dopamine from the synapse. (Demo)