Richard (PNS) Flashcards
Intracellular signalling
2 types:
Electrical
Chemical
- hormones
- neurotransmitters
Divisions of the nervous system
Central nervous system (CNS)
- Brain and spinal cord of dorsal body cavity
- Integration and control centre
- Interprets sensory input and dictates motor output
Peripheral nervous system (PNS)
- The portion of the nervous system outside CNS
- Consists mainly of the nerves that extend from brain and spinal cord
Structure of the PNS
Spinal nerves (31 pairs) to and from spinal cord.
Cranial nerves (12 pairs) to and from brain.
These 43 nerves pairs are considered in terms of structure and function.
Two functional divisions of PNS
Sensory (afferent) division
- Somatic sensory fibres- convey impulses from skin, skeletal muscles, and joints to CNS
- Visceral sensory fibres- convey impulses from visceral organs (soft interior organs) to CNS
Motor (efferent) division
- Transmits impulses from CNS to effector organs- muscles and glands
- Two divisions
- Somatic nervous system
- Autonomic nervous system
Somatic nervous system
Somatic motor nerve fibres.
Conducts impulses from CNS to skeletal muscle
Voluntary nervous system
- Conscious control of skeletal muscles
Autonomic nervous system
Visceral motor nerve fibres.
Regulates smooth muscle, cardiac muscle, and glands.
Involuntary nervous system.
Two functional subdivisions
- Sympathetic- fight and flight
- Parasympathetic- rest and digest
They work in opposition to each other.
(Enteric (GIT) is a 3rd anatomical subdivision)
2 neurones in series
- Pre-ganglionic
- Post-ganglionic
Synapse in an autonomic ganglion.
Post-ganglionic nerves not myelinated.
White matter- carries signals to and from more rostral divisions of the CNS.
Gray matter- where the cell bodies are. Includes the dorsal and ventral horns.
Parasympathetic and sympathetic nervous system
Parasympathetic:
Neurotransmitters
- Acetylcholine
Receptors
- Muscarinic- GPCR
- Nicotinic
Sympathetic:
Neurotransmitters
- Noradrenaline
-Adrenaline
Sympathetic nervous system
Regulates the ‘sympathies’ of the body.
Cell bodies in thoracic and lumbar regions.
Synapse in ganglia in sympathetic chain (sort pre-ganglionic).
Each pre-ganglionic neurone synapse with many longer post-ganglionic neurones.
Main drug targets within the noradrenergic nerve and synapse
Adrenoceptors
- Pre and post junctional
- Directly acting agonists and antagonists
- NE release
Enzymes
- Synthesis and metabolism of NE
- False substrates/transmitters
Carrier molecules
- Uptake 1 (pre-junctional) and uptake 2 (post-junctional)
- NE uptake into storage vesicles
Adrenoceptor sub-classification
Adrenoceptors
- Alpha 1 adrenoceptors
- alpha1a/c
- alpha1b
- alpha1a/d
- Alpha 2 adrenoceptors
- alpha2a/d
- alpha2b
- alpha2c
- Beta adrenoceptors
- beta1
- beta2
- beta3
- beta4?
Not all of these receptors have selective agonists and antagonists
Adrenoceptor sub-classification effect on tissues
alpha1
- Constricts: blood vessels, bronchi, GIT sphincter, uterus, bladder, bladder sphincter
- Relax: GIT
alpha2
- Constricts: blood vessels
beta1
- Relax: GIT
beta 2
- Dilate: bronchi, GIT
Main physiological effect of alpha adrenergic agonists
- Smooth muscle contraction (except GIT)
- Vascular predominantly
- Increase in systolic and diastolic BP
- Increase in peripheral resistance
- Increase in BP and relax bradycardia
- Trophic response- smooth muscle proliferation, cardiac hypertrophy
- Decrease in noradrenaline release
Main physiological effect of beta adrenergic agonists
- Smooth muscle relaxation
- Bronchial tissue and uterus strongly dilated
- Powerful chronaotropic and inotropic effect on the heart
- Glycogenolysis
- Skeletal muscle
- Histamine release from mast cells
- Lipolysis
- Tremor
- Aqueous humour production
beta effects on the heart
Positive isotropy and chronotropy.
Cardiac efficiency is reduced- increased cardiac output and increased oxygen consumption
Arrhythmias
- ventricular fibrilation
beta effects on skeletal muscle
Twitch tension increased in white muscle
- increased speed of contraction
- effects on tetanus
Tremor
- increase in muscle spindle discharge
changes in sarcoplasmic reticular proteins
- increased muscle mass
- clenbuterol
Pre-synaptic adrenoceptors
alpha2 are found on pre-synaptic bulb as they inhibit NA release.
beta2 found on post-synaptic bulb as they facilitate NA release
Adrenoceptor agonists
Selective
- Phenylephrine (a1)
- Clonidine (a2)
- Dobutanime (b1)
- Salbutamol (b2)
Non-selective
- Methoxamine (a1, a2)
- Isoprenaline (b1, b2)
- Adrenaline/noradrenaline (a1, a2, b1, b2)
Parasympathetic nervous system
The parasympathetic pre-ganglionic fibres leaves the CNS in the cranial nerves and from the sacral region of the spinal cord.
Unlike sympathetic ganglia, parasympathetic ganglia lie close to the target site (tissue or organ) and the post-ganglionic fibres often lie entirely in the tissue of the target organ.
Most parasympathetic pre-ganglionic fibres connect with only a few post-ganglionic fibres. This provides an anatomic explanation for their discrete and localised response.
Parasympathetic cholinergic nerve terminal
Vesamicol blocks the uptake of ACh.
Hemicholinum blocks the re-uptake of choline.
Botulinum blocks the release of ACh.Vesamicol blocks the uptake of ACh.
Hemicholinum blocks the re-uptake of choline.
Botulinum blocks the release of ACh.
The neuromuscular junction
Connection between motor neurone and muscle fibre. Chemical synapse between the nerve terminal and the specialised area of muscle cell membrane called the motor end plate.
When an action potential reaches the nerve terminal it causes the voltage gated calcium channels to open allowing Ca2+ into the cell. This causes the release of ACh into the synaptic space. ACh binds to the nicotinic receptors (ligand gated ion channels) on the end plate. Once bound to Ach they open to allow Na+ to enter the cell which depolarises the end plate and generates an action potential. Acetylcholinesterase removes all ACh molecules that do not immediately bind to the receptors. This terminates synaptic activation giving the muscle time to relax and preventing continuous contraction that would result in muscle spasms.
Nicotinic receptors
There are two main receptor types that cholinergic transmitters act on. These are the nicotinic and the muscarinic receptors.
The nicotinic receptor is ionotropic embedded in the cell membrane. It is a protein with 5 subunits.
Nicotinic receptors are found at neuromuscular junctions in skeletal muscles and in autonomic ganglia. At both sites these receptors are post-synaptic.
Some drugs are selective as to which of these receptors they interact with.
Ganglion blocking drugs
They are no longer used.
They have widespread effects due to the fact that they block sympathetic and parasympathetic ganglia.
Trimetaphan is a ganglion blocking drug which competitively blocks ganglionic nicotinic receptors.
Excessive amount of nicotine may also produce a depolarising block at the ganglion.
Muscarinic receptors
Muscarinic receptors are embedded in the cell membrane.
They are members of the GPCR family (metabotropic) having 7 transmembrane segments in their amino acid sequence.
5 muscarinic subtypes (m1-m5).
Slower than nicotinic
3 types functionally
- M1 - neural and gastric
- M2- cardiac
- M3 - glandular and smooth muscle
