CNS Flashcards
2 major types of ion channels in neuronal membranes
- Voltage gated
* Ligand gated (ionotropic receptors)
Transmembrane ion channels regulated by changes in membrane potential
Voltage-gated ion channels
Transmembrane ion channels that are regulated by interactions between
neurotransmitters and their receptors (also called ionotropic receptors)
Ligand-gated ion channels
Channels responsible for membrane depolarization in action potential generation
Voltage Gated Sodium Channels
Plays an important role in both linking muscvle excitation with contraction as well as neuronal excitation with transmitter release.
Voltage Gated Calcium Channels
Role in repolarization of cell membrane after action potential.
Voltage Gated Potassium Channels
G protein-coupled receptors that respond to neurotransmitters either by a direct action of G proteins on ion channels or by G protein-enzyme activation that leads to formation of diffusible second messengers
Metabotropic receptors
Work by activating other proteins called G porteins. They stimulate or inhibit the opening of ion channels in the cell membrane. But they work more slowly than ionotrophic receptors
Metabotropic receptors
Binding site + channel combined. Second messenger-independent Short latency action Rapid responses Postsynaptic
Ionotropic receptors
Excitatory postsynaptic potential. A depolarizing potential change
EPSP
Inhibitory postsynaptic potential. A hyperpolarizing potential change
IPSP
Ability of an administered chemical to mimic the actions of the natural neurotransmitter
Synaptic mimicry
Respond to changes in membrane potential. They are concentrated on the axons of nerve cells and include the sodium channels responsible for action potential propagation. Cell bodies and dendrites also have voltage-sensitive ion channels for
potassium and calcium.
Voltage-gated Ion Channels
Also called ionotropic receptors. Respond to chemical neurotransmitters that bind to receptor subunits present in their macromolecular structure. Neurotransmitters also bind to G protein-coupled receptors (metabotropic receptors) that can modulate voltage-gated ion channels. Neurotransmitter-coupled ion channels are found on cell bodies and on both the presynaptic and postsynaptic sides of synapses.
Ligand-gated Ion Channels
In the case of ligand-gated ion channels, activation (or inactivation) is initiated by the interaction between chemical neurotransmitters and their receptors.
Coupling may be:
(1) through a receptor that acts directly on the channel protein
(2) through a receptor that is coupled to the ion channel through a G protein, or
(3) through a receptor coupled to a G protein that modulates the formation of diffusible second messengers, including:
a) cyclic adenosine monophosphate (cAMP)
b) inositol trisphosphate (IP3)
c) diacylglycerol (DAG),
Excitatory postsynaptic potentials (EPSPs) are usually generated by the
opening of
sodium or calcium channels
Inhibitory postsynaptic potentials (IPSPs) are usually generated by the opening of
potassium or chloride channels
The effects of most therapeutically important CNS drugs are exerted mainly at
synapses
The CNS contains 2 types of neuronal systems:
hierarchical & diffuse
Delimited in their anatomic distribution. Generally contain large myelinated, rapidly conducting fibers. Control major sensory and motor functions
Hierarchical Systems
The major excitatory transmitters in Hierarchical Systems are
aspartate and glutamate
Drugs that affect hierarchical systems often have
profound effects on the overall excitability of the CNS
Broadly distributed, with single cells frequently sending processes to many different areas.
• The axons are fine and branch repeatedly to form synapses with many cells.
• Axons commonly have periodic enlargements (varicosities) that contain transmitter vesicles.
• The transmitters in diffuse systems are often amines (norepinephrine, dopamine, serotonin) or peptides that commonly exert actions on metabotropic receptors.
Diffuse Systems
Drugs that affect Diffuse Systems often have marked effects on such CNS functions a
attention, appetite, and emotional states
Most CNS responses to ACh are mediated by a large family of _____ that lead to slow excitation when activated.
G protein-coupled muscarinic M1 receptors
The ionic mechanism of slow excitation IN ACh involves a
decrease in membrane permeability to potassium.
Example of Acethylcholinesterase inhibitors used in Alzheimer’s disease
tacrine
Example of muscarinic blocking agents used in Parkinsonism
benztropine
Exerts slow inhibitory actions at synapses in specific neuronal systems commonly via G protein-coupled activation of potassium channels (postsynaptic) or inactivation of calcium channels (presynaptic). The D2 receptor is the main subtype in basal ganglia neurons, and it is widely distributed at the supraspinal level.
Dopamine
Drugs that block the activity of dopaminergic pathways include older antipsychotics (eg, chlorpromazine, haloperidol), which may cause parkinsonian symptoms.
Dopamine (eg, chlorpromazine, haloperidol)
Drugs that increase brain dopaminergic activity include
CNS stimulants (eg, amphetamine), and commonly used antiparkinsonism drugs (eg, levodopa)
Excitatory effects are produced by activation of α1 and β1 receptors. Inhibitory effects are caused by activation of α2 and β2 receptors.
Norepinephrine
Give examples of CNS stimulants, monoamine oxidase inhibitors and tricyclic antidepressants that enhance the activity of noradrenergic pathways.
- CNS stimulants (eg, amphetamines, cocaine),
- monoamine oxidase inhibitors (eg, phenelzine), and
- tricyclic antidepressants (eg,amitriptyline)
Most serotonin (5-hydroxytryptamine; 5-HT) pathways originate from cell bodies in the
raphe or midline regions of the pons and upper brainstem
Multiple 5-HT receptor subtypes have been identified and, with the exception of the ____, all are metabotropic.
5-HT3 subtype
Most of the agents used in the treatment of major depressive disorders affect serotonergic pathways
- tricyclic antidepressants,
- selective serotonin reuptake inhibitors
Which may cause severe depression of mood, depletes vesicular stores of both serotonin and norepinephrine in CNS neurons.
Reserpine
Most neurons in the brain are excited by
glutamic acid
Subtypes of glutamate receptors include the N-methyl-D-aspartate (NMDA) receptor, which is blocked by
- phencyclidine (PCP)
- ketamine
NMDA receptors appear to play a role in synaptic plasticity related to
learning and memory
Is an NMDA antagonist introduced for treatment of Alzheimer’s dementia.
Memantine
Is the primary neurotransmitter mediating IPSPs in neurons in the brain; it is also important in the spinal cord.
GABA
receptor activation opens chloride ion channel
GABAa(alpha)
Receptors (activated by baclofen, a centrally acting muscle relaxant) are coupled to G proteins that either open potassium channels or close calcium channels.
GABAb
___ IPSPs are blocked by GABAA receptor antagonists, and ___ IPSPs are blocked by GABAB receptor antagonists.
Fast; slow
Which are more numerous in the cord than in the brain, are blocked by strychnine, a spinal convulsant.
Glycine receptor
