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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