Chapter 2 physiology of the cells - Fudan...
Transcript of Chapter 2 physiology of the cells - Fudan...
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Chapter 2 physiology of the cells
Cell (细胞)——fundamental structural and
functional unit
More than 200 different cell types——carry
out different functions
General function of cell——common features
(本章主要内容)
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The basic structure of cell
Cell membrane (细胞膜):
Cytoplasm (胞浆):organelle(细胞器)
mitochondria(线粒体)、
endoplasmic reticulum(内质网)、
lysosome(溶酶体)
Nucleus (细胞核)
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Chemical structure of the membraneComposition: lipids(脂质)+ proteins(蛋白质)(4:1-1:4)In 70’s of last century, fluid mosaic model
Framework——Lipid bilayerMembrane proteins:
peripheral protein(表面)、integral protein(镶嵌)
glucose——glycoprotein and glycolipid)
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Transmembrane transport——a basic function of the cell membrane
Relatively stable in intracellular composition,
prevent of leaking out of intracellular contents
Transmembrane transport(物质跨膜转运)
Obtain oxygen and nutrients
Exclude metabolites
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Membrane transport:Simple diffusion(单纯扩散)
Membrane protein facilitated transportationsFacilitated diffusion via carrier (transporter)
Facilitated diffusion via ion channel(经通道易化扩散)
Primary active transport (原发性主动转运)
Secondary active transport (继发性主动转运)
Exosytosis(出胞)and endosytosis(入胞)
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Simple diffusionThermal movements: high concentration to low concentration
(concentration gradient across membrane)
Across the membrane: hydrophobic, low MW(O2、CO2, steroid hormone)
Permeability(通透性):
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Carrier or transporter facilitated diffusion (易化扩散)
Driven by concentration gradientFacilitated by specific proteinWithout ATP consumptionSpecial protein:
carrier(载体)transporter(转运体)
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Carrier or transporter facilitated diffusion
Glucose(葡萄糖)、Amino acid(氨基酸).
Characteristics:
Specificity(高度特异)
Saturation(饱和现象)
Competition (竞争抑制)
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Channel facilitated diffusion
Na+、K+、Ca2+、Cl-
Characteristics(compared with carrier or transporter):
1. Transporting speed-fast2. Opening time-short 3. Selectivity-poor4. Precisely regulated
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Classification of the channels
1. Chemically-gated ion channel(化学门控通道)
2. Voltage-gated ion channel(电压门控通道)3. Mechanically-gated ion channel(机械门控
通道)
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Chemically-gated ion channel(化学门控通道)
Na+
ACh receptor
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Voltage-gated ion channel (电压门控通道)
Na+ channel
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Hair cell of cochlea
Mechanically-gated ion channel (机械门控通道)
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Primary active transport(原发性主动转运)
From low concentration to high concentrationFacilitated by special proteinCombined with ATP consumption
Typical example: ion pump (离子泵)Sodium-potassium pumpCalcium pump(钙泵)
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Sodium-potassium pump
• Exist in all cell types
• Coupling ratio: 3 Na+ to 2 K+
• Maintenance of Na+ and K+
distribution
• Activation
• Inhibited by ouabain(哇巴因)
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Secondary active transport(继发性主动转运)
No directly ATP consumption
Renal tubule: glucose, AA are transferred into the cell combined with Na+
Necessity1. Na+: High to low
2. Glucose: Low to high
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Category of Secondary active transportSymport(同向转运)
Na+-glucose symporter
Antiport(逆向转运) exchange (交
换)
Na+-Ca2+ exchanger
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Exocytosis (出胞) and endocytosis (入胞)
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Signal transduction in the body
Intercellular communication: ChemicalElectrical
Transmembrane signal transduction
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Chemically Intercellular communication
telecrine
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Transmembrane signal transductionHepatocyte: glycogen synthesis and break down
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Transmembrane signal transduction
G-protein coupled receptorEnzyme-linked receptorRecruitment receptorIon channel receptorNuclear receptor
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Electrical phenomena of the cell
Bioelectrical phenomena is commonly existed
Heart—electrocardiogram (ECG)Brain—electroencephalogram (EEG)Skeletal muscle—electromyogram (EMG)
Based on electrical activities of specific cells Numbfish
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Measurement of transmembrane potential
Transmembrane potential: the potential difference between the inside and outside of cell membrane
•Amplifier •Cathode ray oscilloscope•Microelectrode
Transmembranepotential
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Resting potential
-90 mV
Depolarization
Hyperpolarization
0 mv
(Polarization)
AB
MP
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Genesis of Resting PotentialIn 1902, Bernstein: K+
equilibrium potential)
Nernst formula
Low rate of sodium influx
Sodium-potassium pump:
5mV
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Action potential
Spike potential
Negative after potential
Positive after potential
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Characters of action potential
Minimal intensity
of stimulation
1. “All-or-none” law
2. Propagable
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Ionic basis of action potentialDepolarizing phase
Inward current-sodium influx
Repolarizing phase
Outward current-potassium
efflux
Spike potential
After potential
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Bursting of action potentialSubthreshold——a few channels——local response (局部反应)
Threshold intensity——Na+>K+——depolarization (positive feedback——Na+
equilibrium potential(AP)
All or none——character
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Threshold stimulus and threshold potential level
Threshold stimulus
(阈刺激)——
minimal stimulus
that can evoke AP
Threshold potential
(阈电位)——firing
level
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Local response and its characters
Subthreshold stimulus——local response
Not “all or none”
Electrotonic propagation
No refractory period
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Characters of local response
Summation
Temporal summation
Spatial summation
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Conductance of Action potential ——circular current (局部电流) theory
Conductance of Action potential
Distance
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Conduction of AP in myelinated fibers
Na+ channels: Nodes of Ranvier, initial segment
Saltatory conduction
Result of evolutionFast
Efficient
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Factors that influence AP conduction
1. Diameter (直径)
2. Velocity(速度)and
altitude(幅度) of AP
1. Driving force of Na+
2. State of Na+ channels
Spike potential
After potential
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Gap junction (缝隙连接)
Connexon channel
connexin
Cell membraneGap junction
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Excitability (兴奋性) and Excitation (兴奋)
Excitability: environmental change——responsesA basic characteristic of life
Excitation (兴奋): appearance, less activity——more activityInhibition (抑制): more activity——less activity
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About excitability(兴奋性)Isolated cell, tissue and organ may still get excited
Neuron, muscle, gland cell——excitable cells(可兴奋细胞)
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Essence of excitationElectrophysiology:
Appearance ——differentAP——same
Excitation ——APExcitability ——the ability to produce AP
Excitability is reciprocal to threshold
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Stimulus (刺激)Definition: the changes in environment that can result in changes in body function.
3 basic elements of stimulusStrength (强度)Duration (持续时间)Changing ratio of strength/duration(强度时间变化率)
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Changes in excitability during action potential
AC: Absolute Refractory period
BC: Relative ~
CD: Supranormal period
DE: Subnormal period
Mem
bran
e P
(mV
)
Action potential
Exc
itabi
lity Excitability
Time
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Factors influence excitability——resting potential
RP↑——
excitability↑
Increase too much——
excitability↓
(threshold↑)
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Factors influence excitability——threshold
Threshold↑——
excitability↓
Factors determine the
threshold
Density of Na+ channel
State of Na+ channel
Local response
Subthreshoud stimuli Subthreshoud stimuli
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Factors that influence the excitability
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Biphasic and Monophasic Action Potentials
Spike potential
After potential
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Contraction of muscle
Classification:Function: skeletal muscle(骨骼肌), cardiac muscle(心肌), smooth muscle(平滑肌)
Morphologic character: striated muscle(横纹肌)、smooth muscle(平滑肌)
Nervous innervations: voluntary muscle (随意肌)、involuntary muscle (非随意肌)
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Skeletal muscle
Transmission of AP at neuromuscular junction
Ultrastructure of muscle cell
Process of contraction
Excitation-contraction coupling(兴奋-收缩耦联)
Factors that influence contraction
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Transmission of excitation
Pre-junctional membrane (接头前膜)
Endplate membrane (终板膜, 接头后膜)
Junctional cleft (接头间隙)
Synaptic vesicle (突触小泡)
Acetylcholine (乙酰胆碱)
Endplate potential (终终板电位)
Quantal release (量子释放)
Miniature endplate potential (微终板电位)
Cholinesterase
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Anatomy and transmission• Myasthenia gravis——destroy
Ach receptors
• Eaton-Lambert syndrome——autoimmune disease, Ca2+
channel in presynaptic m
• Botulin——release acetylcholine
• Curare——ACh receptor blocker
• Organophosphorus pesticides——inhibitor of cholinesterase
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Structure of skeletal muscle• Myofibril (肌原纤维)
• Striation:
•Dark band (暗带)
•Light band (明带),
•M line, Z line, H zone
• Sarcomere (肌节)
• Filament (肌丝):
•Thick
•Thin
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Structure of skeletal muscleSarcotubular system (肌管系统)
T tubule (transverse tubule)L Ca2+ channel
Sarcoplasmic reticulumCa2+ pump
Ryanodine receptor (RYR)
Triads:
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Process of muscle contraction
1954, myofilament sliding theory:
Shorten in sarcomeresNo shorten in FilamentsSliding of thin F over thick F
Observation:Shorten on light B, not dark BShorten on H zone
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Molecular structure of filamentThick filament:
MyosinCross bridge
Thin filament:ActinRegulatory proteins
TropomyosinTroponin
T——TropomyosinI——ActinC——Ca2+
Cross bridge
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Process of contraction
Ca2+↑→binding to troponin →
weaken troponin-actin binding →
→ exposure of myosin binding site
→ hydrolyzing ATP → swiveling
of Cross bridge
Cross bridge cycle
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Excitation-contraction couplingDefinition:depolarizaiton→ ContractionProcess:
AP into T tubuleActivation of L-Ca2+ channelActivation of RYRIncrease in Ca2+
SR release Ca2+:Ca2+ induced Ca2+ releaseDifferent between skeletal and cardiac muscle
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Influences of muscle contraction
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Influences of muscle contraction
Influence factors:Preload (前负荷)After-load (后负荷)Other factors
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Influences of muscle contraction
Influence factors:Preload (前负荷)After-load (后负荷)Contractility (肌肉收缩能力)
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Influence of contractibility of preload
• Preload——initial
length
• Passive tension
• Active tension
• Optimal initial
length (最适初长)
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Optimal initial length?
Optimal initial length——optimal sarcomere length(2.0-2.2
uM)—— maximal cross-linkage number
Arm-wrestling-right posture
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Influence of contractibility by after load
The load- velocity curve
• 0 load——maximal V
• infinity——0
• 1/3 maximal load——
maximal work output
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Other factors
Independent of preload or after load
Neurotransmitters, hormones, diseases, chemicals
NE: Ca2+ Channel opening↑
H+ : compete with Ca2+ ↓
Caffeine: increase sensitivity of Ca2+
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Twitch and tetanus
• Twitch (单收缩)
• Fusion of contraction
• Incomplete tetanus
• Complete tetanus
• In vivo —— Complete Tetamus
• Tetamus —— tension ↑
•AP- all or none
• Minimal tetanizing frequency