12. Autonomic neurotransmitters and physiology of smooth muscle Flashcards
What are the 2 divisions of the central nervous system?
- Sensory division
- Motor division
What are the 2 divisions of the central nervous system?
- Sensory division
- Motor division
What are the 2 subdivisions of motor division in CNS?
- Autonomic nervous system
- Somatic nervous systemm
Which muscles and structures are included in autonomic nervous system?
- Smooth muscle
- Cardiac muscle
- Glands
Which muscle is included in somatic nervous system?
Skeletal muscle
What are the 2 subdivisions of autonomic nervous system?
- Parasympathetic
- Sympathetic
What is the origin of parasympathetic nervous system?
Craniosacral
What is the origin of sympathetic nervous system?
Thoracolumbar
Position of the ganglia of parasympathetic nervous system
Near or in the organ
Position of the organ of sympathetic nervous system
Close to the spinal cord
What is the type of pregangliar axons in both parasympathetic and sympathetic nervous systems?
B type, myelinated
The pregangliar axon in parasympathetic system is ___ (short/long)?
Long
The pregangliar axon in sympathetic system is ___ (short/long)?
short
What is the type of postgangliar axons in both parasympathetic and sympathetic nervous systems?
C-type, unmyelinated
Are the postgangliar axons in parasympathetic nervous system long or short?
Short
Are the postgangliar axons in parasympathetic nervous system long or short?
Long
What is the pregangliar neurotransmitter of parasympathetic nervous system?
Acetyl-choline
What is the pregangliar neurotransmitter of sympathetic nervous system?
Acetyl-choline
(the same thing in parasympathetic nervous system)
What are the postgangliar receptors of parasympathetic and sympathetic nervous systems?
They are nicotine-AchR (neuronal type)
What is the postgangliar neurotransmitter of parasympathetic nervous system? (classic and nonclassic NTs)
- Acetylcholine
- Non-classic neurotransmitters: Vasoactive intestinal peptide (VIP)
- Nitric oxide (NO)
What is the postgangliar neurotransmitter of sympathetic nervous system? (classic and nonclassic NTs)
- Classic: Norepinephrine
- Nonclassic: Neuropeptide Y; ATP
Sympathetic system and parasympathetic systems make up a pathway which is ___
Two-synapse pathway
What is n-AchR? What is the function?
ligand-gated ion channels (Na+/K+)
-> cause rapid depolarization on postganglionic neuron
What is the general role of POSTGGL. NEURON?
Integrate and transfer neural signals to periphery
Nonclassic neurotransmitters can be released at each level of ___
Autonomic nervous system
What type of classic-NT releases that associate with non-classic NTs?
Cotransmission and colocalization
What are the 2 functions of Nonclassic neurotransmitters?
- Cause slow synaptic potential
- Modulate the response
What are the 4 important examples of nonclassic neurotransmitters?
- Vasoactive intestinal peptide (VIP)
- Nitric oxide (NO)
- Neuropeptide Y
- ATP
The role of Vasoactive intestinal peptide (VIP)
- Associate with G-protein-coupled receptors (GPCRs)
(Gs, cAMP↑, relaxation)
What is the role of nitric oxide?
Short-lived gas (NOS; GC activation → lower [Ca2+]IC, relaxation)
Neuropeptide Y colocalizes with ____
Norephinephrine
Neuropeptide Y is released after __
prolonged intense stimulus, contraction
The role of Adenosine triphosphate (ATP) as a nonclassic NT
Acts on purinoreceptors (Ca2+ signal; contraction)
A single axonal branch can influence higher number of ___
targets
What is the pregangliar NT in adrenal medulla?
Acetylcholine
What is the NT receptor on postgangliar neurons in adrenal medulla?
nicotine - AchR (neuronal type)
Which cell starts the Synthesis of epinephrine in the adrenal medulla?
Chromaffin cell
The role of Phenylethanolamine N-methyltransferase (PNMT)?
an enzyme found primarily in the adrenal medulla that converts norepinephrine to epinephrine.
Expression of PNMT depends on ___
high local cortisol level (from adrenal cortex)
How to convert norepinephrine to epinephrine?
Methylation by PNMT
Example: effect of cotransmission of ATP & neuropeptide Y
- ATP produces a rapid contraction of the smooth muscle
- Norepinephrine produces a moderately fast response
- Neuropeptide Y produces the slowest response
Example of Antagonistic effects on the same target at the same time
Example: sinoatrial node in the heart
Sympathetic : NE, E → β1R → heart rate ↑
Parasympathetic: Ach → m2AchR → heart rate ↓
An example of antagonistic effects on different target cells
Example: pupillary size
Sympathetic → constriction in pupil dilator → pupil dilation
Parasympathetic → constriction in pupil constrictor → pupil constriction
An example of similar effects on the same target
Example: secretion of the salivary glands
Sympathetic → thick, viscous secretion
Parasympathetic → watery secretion
An example in which one division has different effect on the same target
Example: sympathetic division on vascular smooth muscle NE → α1R → vasoconstriction
E → β2R → vasodilation (coronary, skeletal muscle)
Examples of sympathomimetic drugs that have direct effects on sympathetic stimulation
- adrenergic receptor agonist (epinephrine, methoxamine)
- α-agonists (phenylephrine)
- β-agonists (isoprotenerol)
Examples of sympathomimetic drugs that have indirect effects on sympathetic stimulation
**Indirect „potentiating effect”
**
- cause release of NE (ephedrine, amphetamine,metamphetamine)
- block NE reuptake (cocaine)
Examples of drugs that have diect effect on Block adrenergic activity
- α-blockers (phentolamine, prazosin)
- β-blockers (propranolol, atenolol)
Examples of drugs that have indirect effect on Block adrenergic activity.
Block synthesis, storage and release of NE (reserpine, guanethidine)
How can sympathomimetic drugs have indirect „potentiating effect”?
- cause release of NE (ephedrine, amphetamine,metamphetamine)
- block NE reuptake (cocaine)
How can drugs have indirect effect that block adrenergic activity?
Block synthesis, storage and release of NE (reserpine, guanethidine)
How can parasympathomimetic drugs have a direct effect on parasympathetic stimulation?
- Ach – short-lived
- muscarinic receptor agonist (pilocarpine)
Example of Parasympathomimetic drugs that have direct effect on parasympathetic stimulation
pilocarpine
How can parasympathomimetic drugs achieve indirect „potentiating” effect in parasympathetic stimulation?
- Inhibit acetylcholinesterase (neostigmine)
- Organophosphate poisoning
- pesticides: parathion, malathion; nerve gases: soman, sarin, novicsok
How can parasympathomimetic drugs achieve effect in blocking cholinergic activity? Give an example
competitive inhibitor of m-AchRs (atropine)
Are the smooth mucle cells multinucleated?
No, they are uninucleated
Are smooth muscle cells striated?
No, they are non-sriated
What is the contractile unit of smooth muscle cells?
sarcomere
Do the smooth muscle cells have L-disk? Why?
No, they don’t have L-disks
-> They have dense bodies
Do the muscle cells have T-tubules?
No
What type of junctions can you find between smooth muscle cells?
- Mechanical junctions
- Functional (electrical, chemical) junctions
Smooth muscle cells contract if ___ (related to Calcium concentration)
The intracellular calcium concentration increases
Ca2+- dependent contraction in smooth muscles
How can IC [Ca2+] rise?
- Ca2+ enters the cytoplasm through channels in caveoli
- Ca2+ release from the sarcomplasmic reticulum
Name of these types of smooth-muscle action potentials
What happen during depolarizing phase?
opening of L-type voltage gated Ca2+ channels
What happen during repolarizing phase?
delayed activation of voltage gated K+ channels
What happen during slow waves (a type of smooth-muscle action potential)?
Ca2+ -dependent K+ channels
Are voltage-dependent Na+ channels necessary in smooth-muscle action potential?
No
Spontaneous electrical activity in some smooth muscle
-> How do Regular, repetitive oscillations: slow waves (interstitial Cajal cells) occur?
What are the 2 types of smooth muscle?
- Multiunit SM
- Single unit (unitary SM)
Name 2 types of contraction
Describe this graph
[Ca2+]IC , cross-bridge phosphorylation and force reach a peak and return to the baseline
Describe this graph
[Ca2+]IC , cross-bridge phosphorylation decline after a peak but do not return to the baseline
-> Latch-state with low energy expedinture
What does this graph indicate?
Contractile activity patterns by different smooth muscles
What are the 2 types of Ca2+ signal?
- Voltage-dependent (depolarizing)
- Voltage-independent (pharmacomechanical coupling)
Where can you find voltage-dependent Ca2+ signal?
- From adjacent cell (gap junction)
- Neuronal skin (NT-induced)
- Mechanical stress (Bayliss-effect)
Where can you find voltage-indepedent Ca2+ signal?
- SR Ca2+ release (sarcomplasmic reticulum) via IP3 pathway and Ca2+ induced Ca2+ release
- Ca2+ rentry through non-voltage-dependent channel
Are action potentials always needed to initiate contractions?
No, they are not.
How does contraction occur?
Ca2+ -> Ca2+ calmodulin complex -> MLCK activation -> Phosphhorylation of MLC20
-> Cause conformational change (ATP-ase activation increase, interaction with actin)
What happen if MLCK/MP activity is high?
MLC-P/MLC increase -> leads to contraction
What happen if MLCK/MP activity is low?
MLC-P/MLC decreases -> leads to relaxation
Why is ratio of MLC-P/MLC important?
It is used to generate force
Make a schematic drawing of contraction and relaxation of smooth muscle cells
Relaxation of smooth muscle cells occur via 2 pathways which are ___
- cAMP pathway
- cGMP pathway
Make a schematic drawing of NO signaling
What are the 3 main components in termination of Ca2+ signal?
- PM Ca2+ - ATPase
- PM Na+/Ca2+ antiporter
- SR Ca2+ - ATPase (SERCA pump)
What are the 3 main components in termination of Ca2+ signal?
- PM Ca2+ - ATPase
- PM Na+/Ca2+ antiporter
- SR Ca2+ - ATPase (SERCA pump)
Sliding filament mechanism
What is Rachet action?
Actin is pulled toward the center
