C2S Theme 6-8: Chemical & Electrical communication Flashcards
1
Q
Compare & contrast the histology of smooth/ skeletal & cardiac muscle fibres
A
Smooth –> spindle/ round central nucleus/ GAP junctions
Skeletal –> spindle, multi peripheral nuclei, cross striations from sarcomeres
Cardiac –> Branching, single pale central nucleus, intercalated discs, cross striations
2
Q
Describe the innervation of skeletal muscles
A
Somatic –> voluntary
3
Q
Describe the innervation of cardiac muscles
A
Autonomic –> involuntary
4
Q
Describe the innervation of smooth muscles
A
Depends if multiunit or visceral…
Multiunit= 1 nerve supplies muscle fibres, functionally independant, never contract spontaneously
Visceral= Bundles of nerve fibres with GAP junctions, contract spontaneously if stretched beyond their capacity
5
Q
Pls give example of multiunit smooth muscle
A
blood vessel walls
6
Q
Give example of visceral smooth muscle
A
GIT smooth muscle
7
Q
Define the A band of the sarcomere
A
Section of myosin filaments that can overlap with actin (interdigitating even when extended)
8
Q
Define the H band of the sarcomere
A
Section of myosin only!
9
Q
Define the I band of the sarcomere
A
Actin only filaments (opposite of H)
10
Q
Define the Z line of the sarcomere
A
Line connecting 2 adjacent sarcomeres. Part of actin.
11
Q
Draw a sarcomere
A
Draw it
12
Q
Describe Type I muscle fibres
A
Skeletal muscle Red muscle cells Thin Inc mitochondria + myoglobin Dec myosin ATPase Slow & sustained contraction e.g. posture
13
Q
Describe Type II muscle fibres
A
Skeletal muscle White muscle fibres Thick Less myoglobin Inc myosin ATPase Fast contraction
14
Q
What are muscle spindles?
A
A bundle of specialised intramural fibres surrounded by a CT capsule that are embedded in the muscle belly and detect stretch to aid perception of stretch/ velocity/ acceleration
15
Q
What are the 3 specialised cell junctions that aid the function of cardiac cells? What do these make up?
A
Fascia adherens
Macula adherens
Gap junctions
Make intercalated discs
16
Q
Describe fascia adherens
A
Structure that anchors actin to the nearest sarcomere
17
Q
Describe macula adherens
A
Desmosomes
Stop separation during muscle contractions
18
Q
Describe gap junctions
A
Cell junction that enables action potentials to spread from cardiac muscle to cardiac muscle
19
Q
What are purkinje fibres?
A
Bundles from the AV node of the heart that bifurcates to travel to the apex of the heart, connecting to cardiac muscles –> facilitating ventricular contraction
Conduct stimuli faster than cardiac muscle fibres
20
Q
What are the 4 classifications of signalling cells
A
Paracrine
Autocrine
Endocrine
Synaptic
21
Q
Define paracrine cells
A
Relating to a substance secreted by a cell with a localised effect on DIFFERENT neighbour cells
e.g. inflammation
22
Q
Define autocrine cells
A
Effect on same cell (or neighbouring cell of same type) from which substance was secreted
e.g. cytokine binds to receptor on same cell
23
Q
Define endocrine
A
Substance that travels to have effect distally
e.g. hormones
24
Q
What are the 7 types of signals? (shit question soz)
A
- Hormones & ligand bonding
- Neurotransmitters
- External environmental factors
- Mechanical (stretch)
- Immunological
- Metabolic
- Dissolved gases
25
What are the 4 classes of hormones?
Peptides/Proteins, Amines, Steroids, Eicosanoids
26
What are ligands used for?
Conduits for receptor activation
27
What is a tropic hormone?
1ary function is regulation of hormone secreting cells/ other endocrine glands
28
What is an example of a tropic hormone
Thyroid stimulating hormone produced by anterior pituitary that causes release of thyroxine
29
What is a non-tropic hormone?
Exerts effect on non-endocrine target tissues
30
What is an example of non-tropic hormones?
Insulin on liver/ muscle/ adipose
31
What is the functional class of peptide hormones? (i.e solubility)
Water soluble (hydrophilic)
32
Describe how hydrophilic hormones bind to target
1. 1st messenger (hormone binds to membrane)
2. Activated receptor --> cascade --> enzyme activation
3. Enzyme --> 2nd messenger
4. 2nd messenger --> response
33
Why do hydrophilic/ lipophilic hormones bind to cells via different mechanisms?
Because hydrophilic hormones can't cross cell membranes by themselves (lipophilic can), they must bind to external membrane receptors and initiate a catalytic enzyme cascade/ G protein coupled receptor that ultimately releases a 2nd messenger (e.g. cAMP) to elicit the response intracellularly!
Contrastingly, lipophilic hormones can diffuse through cell membranes and subsequently bind to intracellular receptors e.g. cytosol or nuclear receptors, activate gene transcription and exert their desired effect on protein synth.
34
What is the ultimate actions of cell surface receptors for hydrophilic hormones?
G protein coupled receptor or catalytic enzyme coupled receptor --> both activate a transduction cascade and stimulate paths leading to gene transcription
35
How are peptide hormones secreted?
Exocytosis
36
What is the "action" of peptide hormones
Ion channel changes
| Second messenger systems
37
What are 3 examples of peptide hormones
Insulin
Glucagon
Angiotensin
38
Describe the hormone class and function of insulin
Peptide
"Store hormone"
Produced in pancreatic B cells
Dec liver gluconeogenesis, inc glycogen synthesis, inc fat retention --> acts on liver/ muscle/ adipose
39
Describe the hormone class and function of glucagon
Peptide
"Mobilise hormone"
Inc liver gluconeogenesis, blood glucose, triglyceride breakdown
40
Describe the hormone class and function of Angiotensin?
Peptide
Na+ & H20 retention
Vasoconstriction
NaCl reabsorption at proximal tubule (via Na+/H+ antiporter, and cAMP drop at GIT)
ADH & aldosterone release as part of RAAAAAAAS
41
How is the peptide hormone insulin regulated?
Pancreatic B cells monitor circulating metabolites (glucose levels) --> parasympathetic stimulation somehow idk
42
What are the two types of amine hormone;?
```
Catecholamines (tyrosine derived)
Thyroid hormones (iodinated forms of tyrosine derivatives)
```
43
List some areas of the bod that peptide hormones are produced
hypothalamus, pituitary, pancreas, parathyroid, kidneys, liver, heart, GI
44
Where are amine hormones produced?
Adrenal medulla
45
Describe the solubility of amine hormones
Catecholamines are water soluble
Thyroid hormones are iodenated forms of tyrosine derivatives --> lipid soluble
46
How are hydrophilic amine hormones transported
Free hormone bound to plasma proteins
47
How are amine hormones secreted ?
exocytosis
48
Where do amine hormones bind?
Cell surface
49
What is the "action" of amine hormones over the general target cell?
Activation of the 2nd messenger system
50
What are two examples of catecholamine hormones?
Adrenaline
| Noradrenaline
51
Describe the action of adrenaline
```
Produced in adrenal medulla
Inc glucose & FAs in blood to inc energy
Dilate BV
Glycogenolysis
Inc glucagon synthesis
Inc lipolysis
```
52
Describe the action of noradrenaline
Constrict BV
| inc skeletal muscle contraction and HR
53
Describe the solubility of thyroid hormones
Lipid soluble
54
How are thyroid hormones stored & transported?
Stores as thyroglobin in colloids --> cleaved to active T3, T4
Transported bound to plasma proteins
55
What is the target receptor and action of thyroid hormones?
Inside target cell
Direct effect on genes
56
What is the function of thyroid hormones?
Growth (e.g. bone maturation)
BMR (inc metabolic rate, O2 consumption, nutrients, heat production)
Metab (inc glucose use & mobilisation, inc lipolysis & protein catabolism)
57
What are the steroid hormones derived from?
Cholesterol
58
What are the 4 areas where cholesterol hormones are produced from (+ match w/ hormone)
1. Adrenal cortex (cortisone, androgens, aldosterone)
2. Ovaries (oestrogen, progesterone)
3. Testes (testosterone)
4. Placenta (oestrogen and progesterone)
59
What is the solubility of cholesterol hormones?
Lipophilic
60
Describe the storage and transport of cholesterol hormones
Bound to plasma proteins
Not really stored, only cholesterol precursor stored
61
How are cholesterol hormones secreted?
Via diffusion
62
What is the general target of cholesterol hormones?
Inside cell target
63
What are two examples of steroid hormones
Aldosterone and cortisol
64
What is the action of aldosterone
Reabsorb Na+ to inc BV
65
What is the action of cortisol
Defence against hypoglycaemia --> anti-inflammatory actions
66
Describe the two feedback mechanisms of cortisol
- ve feedback (long feedback) at pituitary and hypothalamus
| - ve feedback (short loop) straight to hypothalamus by ACTH
67
What are the 4 types of eicosanoid hormones
1. Prostaglandins
2. Prostacyclins
3. Thromboxanes
4. Leukotrines
68
Which cells produce eicosanoids
most cells except erythrocytes!!
69
What is the solubility of eicosanoids
water soluble
70
What is the general cell target of eicosanoids
Cell membrane
71
What is the general effect of eicosanoid after binding to target
Activation of 2nd messenger system, in particular the G protein coupled fam
72
What I the functions of prostaglandins
Vasodilators
73
What is the function of leukotrienes
Allergy
Vascular permeability
Neutrophil chemo-attractant
74
What is the funcito n of thromboxane
Platelet aggregation
| Vasoconstriction
75
What determines the level and duration of hormone secretions
Feedback loops --> changes rate of production and secretion
Lifespan in blood --> metabolic inactivation, excretion, extent of plasma protein binding
Number & sensitivity of receptors (cause up and down regulation
76
What are 3 mechanisms by which endocrine disfunction might lead to disease ?
1/ increased or reduced activity of hormones
2. inc removal from blood/ bad transport
3. transduction failure (e.g. adequate hormone but cells don't respond)
77
What are 4 mechanisms that might cause inc/dec activity of hormones
1. Tumour (e.g. thyroid tumour inc T43, pituitary tumour inc cortisol [cushing's disease])
2. Immune (type 1 diabetes from dead pancreatic islet cells)
3. Genetic (enzyme absence)
4. Dietary deficiency
78
What are the 4 types of cell receptors for hormones
1. Kinase linked
2. G coupled protein receptor
3. Ligand gated ion channel
4. nuclear receptors
79
Describe how ligand gated ion channels work
an ion channel opens or closes in response to a binding ligand e.g. acetylcholine
80
How quick do ion channels work
milliseconds
81
What is an example of a ligand gated ion channel receptor ?
nicotinic ACh receptor
82
What is the difference between ionotropic and metabotropic ion channels?
Ionotropic = nicotinic
- ion channel
- opens Na+ channel for depolarisation --> skeletal muscle contraction
Metabotropic = muscarinic
- G protein activated --> opens K+ channel for membrane hyperpolarization
83
Order the speed of the 4 types of endocrine receptors
Fastest - slowest
Ligand gated ion channel (milliseconds) > G protein coupled > kinase linked > nuclear (mins-hrs)
84
Describe how G protein coupled receptors function
1. ligand bonds to exterior GPCR
2. GPCR undergoes conformational change where A subunit moves away from B, Y subunit (via dissociation).
3. A binds to one receptor enabling B+Y bind to another.
4. A subunit changes ion channels to change excitability (I think?!) --> releasing Ca++ --> cell effects
5. B+Y dimer activates enzyme to produce a 2nd messenger that causes protein phosphorylation --> cell effects
6. Hydrolysis reverts back to normal
85
Describe how the ligand epinephrine binds to GPCR to elicit tis functions
1. Binds to GPCR (adrenergic receptor)
2. conformational change of GPCR
3. A subunit regulates functions of adenylyl cyclase (i.e takes ATP and makes it cAMP)
4. cAMP is the 2nd messenger which can intracellularly exert effects
^ HR
dilate skeletal muscle BV
^ Blood glucose
86
Describe kinase linked receptors
They are cytokine receptors where the receptor is an enzyme. The cytokine binds to the enzyme --> protein phosphorylation --> gene transcription --> protein synth --> cell effects
87
Describe how intracellular (nuclear) receptors function
regulate expression of target genes by binding to specific DNA sequences
Either at cytoplasm (cortisol, aldosterone)
Nucleus (thyroid)
88
Endocrine cells secrete stuff in response to...
ions, nutrients, neurotransmitters, other hormones
89
What are the two types of feedback loops for hormones ?
1. -ve feedback driven by physiological response
- -> endocrine gland --> hormone --> target organ = physiological effects --> circulating component e.g. blood glucose --> causes -ve feedback to endocrine gland
2. Endocrine axis driven
- -> Hypothalamus neurons --> RELEASE HORMONE --> pituitary gland --> TROPIC HORMONE --> peripheral endocrine gland --> HORMONE --> target organ --> physiological effect.
Hard to explain in a flashy but at the (peripheral) HORMONE level --> short arm -ve feedback acts on pituitary gland and long arm -ve feedback acts on the original hypothalamus neutrons
90
Briefly describe how hormones can act additively with e.g.
Both glucagon and adrenaline act on Gs proteins (a class of GPCR receptor) to form adenylyl cyclase --> which is turned into a lot of cAMP and activates SAME enzymes (with an additive effect cause its double)
91
How does cholera toxin exert its effect and on which type of receptor
Toxin --> blocks the subunit of GPCR that usually activates adenylyl cyclase so the GPCR can no longer hydrolyse GTP (subunit of the GPCR) so there is no conformational change of the GPCR and nothing can bind!
92
What is the role of nitric oxide signalling
signalling molecule in cardiovascular system --> role in controlling blood flow and pressure.
Acts on vascular endothelial cells --> vasodilation
93
Which cells have resting membrane potentials?
all cells
94
Name 4 features of action potentials
1. unidirectional
2. do not lose amplitude along an axon
3. messages capable of being sent long distances
4. message intensity sent via frequency of action potentials
95
What is the refractory period ?
The short time interval when the axonal membrane is no longer receptive to stimulus
96
What factors influence the velocity of transmission of information along a two-chain neuron network?
```
Myelination
larger axon (more ions)
```
97
Which molecules cause the release of NOs
ACh, Bradykinin, adenine nucleutides
98
Which intracellular mechanism causes the release of NO, and from which cells> ?
NO synthase is activated by (ACh, bradykinin, adenine) to produce NO which is released from endothelial cells
99
State the steps by which NO is synthesised, released from endothelial cells
1. ACh binds to Gq protein linked receptor on endothelial cell
2. Ca++ released from ER
3. NO synthase converts arginine to NO
4. NO diffuses from endothelial cells
6. Makes cGMP (2nd messenger)
5. Acts on smooth muscle
7. Short T1/2 and breakdown to nitrates/ nitrites stops effect
100
What is a clinical use of NOs?
Viagra (Put me in the clinic)
| --> blocks degradation of 2nd messenger cGMP so the NO signal is prolonged WOOOOOOO ;)
101
What are 5 key aspects of hormone signalling via cell surface receptors
1. Specficity (e.g. ligand bonding)
2. Amplification (e.g. because 1st messenger is short lived, 2nd intracellular messenger amplifies effect)
3. Integration (e.g. pathways that provide reciprocal response to signals
4. Rapid decay (e.g. allows short term/ reversibility)
5. Desensitisation (e.g. achieved by feedback loop to reduce effect when appropriate)
102
Where is K+ higher (ICF/ECF)
ICF
103
Where is Na+ higher (ICF/ECF)
ECF
104
Where is Cl- higher (ICF/ECF)
ECF
105
What type of gradient drives K+ out of cell?
conc gradient
106
What type pf gradient pulls K+ back into cell?
electrical conc/ membrane potential formed by cell becoming more -ve as K+ leaves via ion channels
107
Via what transport system does K+ leave cell?
Ion channels via diffusion down conc gradient
108
Via what transport system does Na+ enter cell?
Voltage gated ion channels (threshold -50mv )
109
What stops the cell reaching its threshold value for K+ (which is ~-90mV) whilst all dat K+ is leaving down its conc gradient??
Small amounts of Na+ are brought into cell to stop ICF from becoming too -ve. They come in via the Na+/K+ ATP-ase pump, which maintains the RMP
110
Which membranes can facilitate AP production?
Excitable membranes e.g. of nerves/ muscle cells (sarcolemma)
111
What does the membrane potential change from during production of an AP?
-70mV > -50mV (reaches threshold here) > +30mV (polarisation) > ~-80mV (hyper polarisation) > -70mV (RMP)
112
What is important about the conformational channel change at the peak of polarisation?
Na+ channels close so no more can enter!
K+ channels open so that RMP can be reinstated
Na+/K+ ATPase channel pumps 2Na+ out for every 2K+
113
Why does hyper polarisation occur?
K+ are open so more K+ leaves cell than necessary (making cell more -ve and further from threshold) (i.e value below -70mV)
114
What is the absolute refractory period?
time when Na+ permeability changes
115
What is the relative refractory period?
Time when K+ permeability changes
116
What are the 3 types of graded potentials
1. Synaptic
2. Receptor
3. Pacemaker
117
What determines the effect of neurotransmitters at a post synaptic membrane?
Synapse --> excitatory or inhibitory!
| Strength of AP
118
How does an excitatory membrane do its thang ?
INC permeability to na+, K+ :D
Na+ flows down conch gradient + electrical gradient --> NET +ve ions into post synaptic cell --> brings membrane potential closer to threshold
119
How do an inhibitory membrane work!? ?! !? ! ?!?
INC permeability to K+ or Cl- :(
So lessens likelihood of reaching threshold
Closer to hyperpolarisation
120
Name 4x types of neurotransmitters pls
ACh,
Catecholamines
glycine
GABA
121
Tell me about ACh
Neurot. from neuromuscular junction @ skeletal muscles
1. Synthesised as postsynaptic axon when acetyl CoA --> acetyl choline via choline acetyltransferase)
2. released quantally (in little packages) when enough AP affects snare proteins and allows exocytosis from presynaptic terminal
3. AChE hydrolyses ACh to dec conc
122
Tell me about adrenaline & noradrenaline
Neurot. from sympathetic junctions @ smooth muscles (also act as hormones in blood)
Noradrenline acts of forebrain (influencing attention etc) adrenaline not really known
123
Why do APS have no effect at post synaptic neuron body (until axon hillock)? What type of AP are they?
Graded potential --> no polarisation effect because axon body has min ion channels
Axon hillock has plenty of voltage gated ion channels so can reach threshold
124
Does ACh acting on a nicotinic receptor elicit an excitatory or inhibitory response
Excitatory --> increases Na+ permeability so brings membrane closer to threshold
125
Does ACh acting on a muscarinic M1 receptor elicit an excitatory or inhibitory response
Excitatory --> Dec K+ permeability so brings membrane closer to threshold (i.e less K+ leaving = ICF more +ve and closer to -50mV)
126
Does ACh acting on a muscarinic M2 receptor elicit an excitatory or inhibitory response
Inhibitory --> Inc K+ permeability so brings membrane further from threshold (i.e cell becomes more +ve)
127
How can neurotransmitter ACh elicity an excitatory OR inhibitory effect at the neuron?
Depends on the type of the receptor at the post synaptic membrane!
Nicotinic/ Muscarinic (M1 vs. M2)
128
What is the effect of botulinum toxins and Sarin?
Botulinum --> protease toxin that interferes with snare proteins that usually let vesicles travel to synaptic cleft. NO neurotransmission!
Sarin --> similar to OPs, AChE inhibition so can't mop up neurotransmitter in synaptic cleft.
129
Where does ACh bind to its receptors in skeletal muscles innervated by a nerve fibre?
Motor end plate
130
How does AP travel into sarcoplasm of muscle cell
T tubule (continuation of the sarcolemma into the sarcoplasm)
131
Outline the role of Ca++ in muscle contraction
1. muscle AP propagated along sarcolemma into sarcoplasm via T tubule
2. Ca++ released from SR
3. Ca++ binds to troponin to remove blocking action of tropomyosin
4. Cross bridge forms and moves to slide actin over mysosin
65. Ca++ leaving troponin restores tropomyosin blocking actin w/ Ca++ sequestration
132
Describe how APs etc change cause muscle relaxation
1. AP stops
| 2. ca++ requested from sarcoplasm --> net movement into sarcoplasmic reticulum via Ca++ ATPase pump
133
What are the 3 roles of ATP in muscle contraction and relaxation????
1. energy for movement of cross bridge (actin sliding over myosin)
2. binds to myosin head to break cross bridge
3. Drives Ca++ ATPase pump that sequests Ca++ to aid process of relaxation .. so even to relax uses energy!
134
What happens when muscle runs out of ATP
can't relax --> rigor mortis
135
What are the 3 modes of energy metabolism in skeletal muscle contraction?
1. (initial 10sec) stores of creatinine phosphate that is broken by CK to form ATP
2. Glycolysis --> break down glycogen into glucose --> glycolysis --> TCA (aerobic)
Oxygen deprivation --> anaerobic glycolysis --> lactic acid builds up and is slowly converted back to glucose via the liver (aerobic TCA continues in background)
3. B-oxidation --> FA's broken into Acetyl CoA which goes through TCA to produce ATP
136
What is the difference between Golgi tendon organs and Muscle spindles?
Muscle spindles are embedded deep in muscles to detect stretch, Golgi tendon organs are present in tendons to report tension.
137
Describe the nerve supply of a muscle spindle
Y motor neuron = efferent neuron innervating intrafusal fibres
A motor neuron = innervating extrafusal fibres
138
How does a muscle spindle detect stretch and describe the activation of the neurons
Co activation of Y and A neurons.
| The more or the faster the muscle is stretched, the greater the rate of neuron firing
139
Describe what occurs between the neurotransmitter and the post synaptic membrane to elicit an EXCITATORY response
Binding of ligand --> inc permeability to Na+, Ca+ --> E.g. Na+ flows down conc gradient --> NET +ve ions into post synaptic cell --> brings membrane potential closer to threshold (At axon hillock so can reach threshold!)
140
Describe what occurs between the neurotransmitter and the post synaptic membrane to elicit an INHIBITORY response
Binding of ligand --> inc permeability to K+, Cl- --> lessens likelihood of reaching threshold b/c neurotransmitter binding causes membrane to become more -ve so is further from threshold
141
Name 4 types of neurotransmitters
1. ACh
2. Noradrenaline/Adr
3. GABA
4. Glycine
142
Tell me a lil about ACh
Acts at neuromuscular junction at skeletal muscle
NT for pre-ganglionic fibres of ANS
Synthesised at presynaptic axon
Acts on both nicotinic & muscurinic
Formed via acetyl CoA --> choline via choline acetyltransferase
Released quantally in vesicles
Released when voltage gated Ca++ enter presynaptic terminal, changes snare proteins to enable vesicle release via exocytosis
AChE hydrolysed via acetylcholinesterase to clean up cleft
143
Tell me a lil bit about noradrenaline
Acts at neuromuscular junctions of smooth muscles
Synthesized by tyrosine --> LDOPA --> dopamine (@ nerve) --> NA (@ vesicle) +/- --> Adr (@ adrenal gland if needed!)
NT for post-ganglionic fibres of ANS
Turned into Adr when sympathetic nerves stimulate the adrenal medulla for production
144
Tell me a tiny bit about Glycine & GABA
They inhibit generation of APs at CNS by opening Cl- channels
145
What is the response of a Nicotinic EPSP post synaptic membrane?
INC Na+ permeability to move membrane closer to threshold
146
What is the response of a Muscurinic EPSP to the bonding of ACh?
M1- DEC K+ permeability, membrane moves closer to threshold e.g. GLAND
147
What is the response of a Muscurinic IPSP to the bonding of ACh?
M2- INC K+ permeability, membrane further from threshold e.g. CARDIAC
148
What is the effect of botulinum toxins?
Protease toxin interferes with snare proteins that usually let vesicles travel to synaptic cleft. Vesicles can't migrate to the cleft --> NO transmission of AP
149
What is the effect of sarin?
Opposite of Botulinum.
| Inhibits AChE, similar to action of OPs
150
What occurs at synapses during skeletal muscle relaxation?
1. AP stops
2. Ca++ ATPase pumps back to SR
3. AChE mops up @ cleft
151
What are the 2 sources of ATP for muscles
1. Creatinine phosphate
2. Glycolysis + TCA
3. B oxidation
152
Where is the very initial energy derived from for skeletal muscle contraction?
Creatinine phosphate that is broken via CK
153
What is the 2nd type of energy metabolism recruited for skeletal muscles during early exercise
Glycolysis (aerobic, set amount stored in muscles, then received from blood) then glycolysis (anaerobic, lactic acid converted back to glucose via liver). Can occur concurrently, one is for long term sustainability & the other short term
Also B-oxidation at the same time? IDK
154
Describe the process of B oxidation
FAs --> Acetyl CoA --> TCA (dependant on O2)
155
What is the difference in how contraction of cardiac muscle is facilitated compared to skeletal muscle?!
- Contraction not initiated by neuronal input, only influenced by
- Cells are electrically coupled (pacemaker cells are self excitatory)
- Long APs
156
Describe excitation- contraction coupling in Cardiac fibres
AP spreads along plasma membrane down T tubules, opens voltage gated ion Ca++ channels in T tubules, Ca++ comes in from extracellular environment (no SR) --> facilitates cross bridge cycling
157
How does Ca++ enable contraction of smooth muscle cells
changes the shape of myosin (there is no troponin to bind to!), allowing actin to bind
158
Describe the excitation- contraction coupling in smooth muscles
^ cytosolic Ca++ > Ca++ binds to calmodulin in cytosol > Ca++ calmodulin complex binds to myosin kinase > Myosin kinase uses ATP to phosphorylate myosin cross bridges > Phosphorylated cross bridges bind to actin filaments > cross-bridge cycling production tension & shortening
159
What are Golgi tendon organs?
Situated at muscle-tendon junctions to detect tendon tension as a result of muscle contraction
160
What are muscle spindles vs Golgi tendon organs?
detect muscle stretch, GTOs detect tendon tension
161
How do GTOs enable reflexes and the control of muscle activity
INC tension stimulates sensory receptor --> GTO stretch releases AP --> EXCITATION, signal travels from local reflex circuitry (sensory neurons) --> AP to SC, sensory neurons synapse directly with A motor neurons --> conduct AP back to muscle, causing it to contract and resist being stretched **Control via -ve feedback by means of local spinal reflexes
162
What does the antagonist muscle do in the situation of a stretch reflex to allow the reflex to occur?
Reciprocal innervation allows the relaxation of the antagonist muscle
Interneuron is present to convert the signal from A receptors to inhibitory message for the relaxation of the antagonist muscle in the stretch reflex.
163
How does selectivity for molecular targets lead to specific drug action
As determined by receptor/ molecular targets (e.g. full/ partial agonist, antagonist)
164
What is the EC50?
Potency of the drug i.e how much you need, measured by the ability to shift the agonist on the curve thing
165
What is the Emax?
efficacy of the drug= ability to switch on a response
166
What is drug affinity?
Likelihood to bind to target
167
What is the action of a drug agonist?
Mimic endogenous molecules that would produce that effect
168
What is the action of a drug antagonist
Inhibits endogenous (agonist) molecules by binding competitively --> agonist must be present in the system!
169
What is drug clearance?
Irreversible removal
170
What are the main adrenergic NT's?
Adr, NA, dopamine
171
What are the main cholinergic NT's?
Ach
172
What are metabotropic receptors?
Muscarinic receptors
173
How do muscarinic receptors convert NT's to produce a response
Activation of 2nd messengers
174
On what tissues are muscarinic receptors??
Smooth muscle & glands
175
Why can amplification occur in muscarinic receptors?
Amplification can occur with 2nd messengers facilitated intracellular cascades. This 'magnification' enables the signals to be more systemic/wide spread but a lil slower
176
What are ionotropic receptors?
nicotinic
177
How does a nicotinic receptor interact with a NT to produce an intracellular response
Ligand binds to open ion channels
| Excitatory/ inhibitory depends on ion coming in
178
Where are the 2 types of nicotinic receptors found?
```
Skeletal muscle (Nm)
Neural/ Ganglia (Nn)
```
179
Name 2 nicotinic agonists
ACh, Nicotine
180
Name 2 nicotinic antagonists
d-tubocurarine (neuromuscular blocker)
| Hexamethonium (ganglia blocker)
181
What are the muscurinic receptors?
5x GPCRs
| e.g. M3, M2
182
Where are M3 receptors found
Smooth muscle & glands
183
Where are M2 receptors found
Cardiac muscle
184
Name 2 muscurinic agonists
Pilocarpine (tx glaucoma)
| Carbachol (tx GIT paralysis)
185
Name 2 muscurinic antagonists
Atropine (dec secretions, inc HR and cause bronchodilation)
| Hyoscine (treatment of motion sickness)
186
Where are A1 adrenoceptors found?
Blood vessels, GIT, pupils
187
Where are A2 adrenoceptors found?
nerves
188
Where are B1 adrenoceptors found?
Heart, kidney, liver
189
Where are B2 adrenoceptors found?
Skeletal BV, bronchi
190
How does activation of A1 receptors activate organs?
BV constrict
GIT constrict
pupil constrict
191
Name 4 A1 receptor agonists
Phenylephrine
NA
DA
Epinephrine
192
Name 2 A1 antagonists
Phentolamine
| Prazosin
193
How does activation of A2 receptors activate its target organs?
Inihibition of NT release from nerves
194
Name 5 A2 receptor agonists
Clonidine, Xylozine, NA, DA, epinephrine
195
Name 2 A2 receptor antagonists
Phentolamine
| Yonimbine
196
How does activation of B1 receptors activate its target organs?
Heart - INC HR, INC CO
Kidney- Renin
Liver - Glycolysis
197
Name 2 B1 agonists
Isoprenaline
| Dobutamine
198
Name 2 B1 antagonists
Propanolol
199
How does activation of B2 receptors activate its target organs?
Skeletal BV dilate
| Bronchi dilate
200
Name a B2 agonist
Salbutamol
201
which receptor is NA most efficient at acting on?
A1 > B1 ~ A2 >> B2
202
Which receptor does NA have worst affinity for?
B2
203
Which receptor does Adr have highest affinity for?
B2 ~ B1 ~ A1 > A2
204
Which receptor does Adr have worst affinity for?
A2
205
Which G protein does A1 activate?
Ga
206
Which G protein does A2 activate ?
Gi
207
Which G protein does B1 activate ?
Gs
208
Which G protein does B2 activate ?
Gs
209
Describe the ligand bonding/2nd messenger/ enzyme cascade of A1 adrenoceptors
A1 --> Ga --> Phospholipase enzyme --> IP3, DAG
210
Describe the ligand bonding/2nd messenger/ enzyme cascade of A2 adrenoceptors
A2 --> Gi --> Adenylyl cyclase --> DEC cAMP
211
Describe the ligand bonding/2nd messenger/ enzyme cascade of B1 adrenoceptors
B1 --> Gs --> Adenylyl cyclase --> INC cAMP
212
Describe the ligand bonding/2nd messenger/ enzyme cascade of B2 adrenoceptors
B2 --> Gs --> Adenylyl cyclase --> DEC cAMP
213
What are the 4 types of cholinergic receptors (we know)
Muscurinic --> M2, M3
| Nicotinic --> Nm, Nn
214
Describe how ligand bonding causes a decrease in HR in M2 receptors
Ligand bonds to GPCR Gi --> Gi acts via adenylyl cyclase enzyme --> DEC cAMP, DEC K+ channels (NET inhibitory) --> DEC HR
215
Describe how ligand bonding causes stimulation of smooth muscles and glands in M3 receptors
Ligand bonds to GPCR Gq --> Gq acts via phospholipase C enzyme --> INC IP3 (INC Ca2+ for INC GIT contraction & secret) & INC DAG (protein kinase C)
