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Chapter 4Chapter 4

THE CELL AND TIS THE CELL AND TIS REGULATORY MECHANISMSREGULATORY MECHANISMS

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THE CELLTHE CELL

Among the major advances of the 20th Among the major advances of the 20th century were the discoveries of the century were the discoveries of the structure of DNA and the genetic code.structure of DNA and the genetic code.

The aim of this chapter is to give a short The aim of this chapter is to give a short overview of the basic structure of a overview of the basic structure of a mammalianmammalian （哺乳动物） （哺乳动物） cell and its cell and its possible strategies for adapting to new possible strategies for adapting to new challenges.challenges.

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The Cell is The basic unit of the body

to carry out and control the functional processes of life.

Contained within a limiting membrane

consists of various organelles suspended in cytoplasm.

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General Subdivisions of a CellA. Nucleus (regulatory center of the cell)

B. Plasma Membrane (selectively permeable boundary between the cell and the environment)

C. Cytoplasm (everything between the plasma membrane and the nuclear compartment)

Organelles are individual compartments in the cytoplasm

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Basic Physiological Function of the Basic Physiological Function of the CellsCells

Transport across the cell membraneTransport across the cell membrane

Bioelectrical phenomena of the cellBioelectrical phenomena of the cell

Contraction of muscleContraction of muscle

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Section 1Section 1

Transport of Ions and Transport of Ions and Molecules through the Molecules through the Cell MembraneCell Membrane

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I ReviewI Review

The Cell MembraneThe Cell Membrane

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What do membranes do?

Act as a barrier AND… Receive information Import/export molecules Move/expand

Membranes are Active Dynamic !

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The Cell Membrane System

Membranes surrounding the cell

Membrane systems inside the cellThe nucleus, endoplasmic reticulum, golgi apparatus,

Endosomes ( 内小体） and lysosomes form the endomembrane

（内膜） system

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Composition of the cell membraneComposition of the cell membrane

Protein 55%Protein 55% PhospholipidsPhospholipids   磷脂磷脂

25%25% CholesterolCholesterol 胆固醇胆固醇

13%13% Other lipids 4%Other lipids 4% Carbohydrates 3%Carbohydrates 3%

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LipidsThe structural framework of the cell membrane, approximately 5 nm thick, is a double layer of lipid molecules. Amphipathic （由两性分子构成的）

Spontaneously 自然地form lipid bilayers

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Lipids are amphipathic   由两性分子构成的

Polar

Non

pola

r

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Lipids spontaneously form structures

A lipid bilayer is a stable, low energy structure Self sealing 封闭 structure/eliminate free edge

What drives this structured association?

Exclusion of Lipids from Water… not lipid association

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Lipid bilayers will form closed structures

compartments behave as 2D

fluids Self seal if

disrupted

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Lipids are effective barriers to some compounds

hydrophobic compounds can reach equilibrium quickly

“unfavored” compounds can be

brought across by transport proteins

Need for …..TransportMechanisms

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Proteins in Membrane Bilayer

Types: Integral 整合 - Transmembrane:

ionic channel, ionic pump, carrier, controller (G protein)

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Integral proteins

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Proteins in Membrane Bilayer

Types:

Peripheral 表面 – Lipid anchored and Protein anchored, located mainly at the inside of membrane surface: enzymes, controllers

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Membrane Carbohydrates: Small amounts located at the extracellular surface. in combination with membrane proteins or lipids

glycoproteins or glycolipids. Functions:

Negatively charged, let the cell to repel negative objects Attach cells one to another Acts as receptor substance for binding hormone such as

insulin （胰岛素） Participate in immune reaction as antigen

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II Transport Mechanisms II Transport Mechanisms Through the Cell MembraneThrough the Cell Membrane

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Categories of Transport Across the Categories of Transport Across the Plasma MembranePlasma Membrane

Cell membrane is selectively permeable to some Cell membrane is selectively permeable to some molecules and ions.molecules and ions.

Mechanisms to transport molecules and ions Mechanisms to transport molecules and ions through the cell membrane:through the cell membrane: Non-carrier mediated transport.Non-carrier mediated transport.

Simple Diffusion.Simple Diffusion. 简单简单扩散扩散 Facilitated Diffusion:Facilitated Diffusion: 协助协助扩散扩散

Via CarrierVia Carrier ChannelChannel

Voltage, Chemical and Mechanical gating channelVoltage, Chemical and Mechanical gating channel

Active TransportActive Transport 主动主动转运转运

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Categories of Transport Across the Categories of Transport Across the Plasma MembranePlasma Membrane

May also be categorized by their energy May also be categorized by their energy requirements:requirements:Passive transport:Passive transport: 被动转运被动转运

Net movement down a concentration gradientNet movement down a concentration gradientdoes not need ATPdoes not need ATP

Active transport:Active transport:Net movement against a concentration gradientNet movement against a concentration gradientneeds ATPneeds ATP

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1. Simple Diffusion1. Simple Diffusion

Molecules/ions are in constant state of Molecules/ions are in constant state of random motion due to their thermal energy.random motion due to their thermal energy.

Simple diffusion occurs Simple diffusion occurs whenever there is a concentration difference whenever there is a concentration difference

across the membrane across the membrane the membrane is permeablethe membrane is permeable to the diffusing to the diffusing

substance.substance.

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Simple Diffusion Through Simple Diffusion Through Plasma MembranePlasma Membrane

Cell membrane is permeable to:Cell membrane is permeable to: Non-polar molecules (0Non-polar molecules (022). ).

Lipid soluble molecules (steroids). Lipid soluble molecules (steroids). Small polar covalent bonds (C0Small polar covalent bonds (C022).).

HH220 (small size, lack charge).0 (small size, lack charge).

Cell membrane Cell membrane impermeableimpermeable to: to: Large polar molecules (glucose).Large polar molecules (glucose). Charged inorganic ions (NaCharged inorganic ions (Na++).).

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Rate of DiffusionRate of Diffusion Speed at which diffusion occurs.Speed at which diffusion occurs.

Dependent upon:Dependent upon:The magnitude of concentration gradient.The magnitude of concentration gradient.

Driving force of diffusion.Driving force of diffusion.

Permeability of the membrane.Permeability of the membrane. Neuronal plasma membrane 20 x more permeable to KNeuronal plasma membrane 20 x more permeable to K++ than than

NaNa++..

Temperature.Temperature. Higher temperature, faster diffusion rate.Higher temperature, faster diffusion rate.

Surface area of the membrane.Surface area of the membrane. Microvilli increase surface area.Microvilli increase surface area.

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2 2 Facilitated DiffusionFacilitated Diffusion

Definition: Definition: the diffusion of lipid insoluble or water the diffusion of lipid insoluble or water

soluble substance soluble substance across the membrane across the membrane down their concentration gradients by aid down their concentration gradients by aid

of membrane proteinsof membrane proteins (carrier or channel)(carrier or channel)

Substances: K+, Na+, Ca2+, glucose, Substances: K+, Na+, Ca2+, glucose, amino acid, urea etc.amino acid, urea etc.

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2. Facilitated Diffusion2. Facilitated Diffusion

2.1 2.1 Facilitated diffusion via carrierFacilitated diffusion via carrier 2.2 Facilitated diffusion through 2.2 Facilitated diffusion through

channelchannel 2.2.1 Voltage-gated ion channel2.2.1 Voltage-gated ion channel 2.2.2 Chemically-gated ion channel2.2.2 Chemically-gated ion channel 2.2.3 Mechanically2.2.3 Mechanically 机械机械 -gated ion -gated ion

channelchannel 2.2.4 Water channel2.2.4 Water channel

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2.1 Facilitated Diffusion via carrier2.1 Facilitated Diffusion via carrier

Concept: Diffusion Concept: Diffusion carried out by carrier carried out by carrier proteinprotein

Substance: glucose, Substance: glucose, amino acidamino acid

Mechanism: a “ferry” Mechanism: a “ferry” or “shuttle” processor “shuttle” process

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Facilitated Diffusion via CarrierFacilitated Diffusion via CarrierCharacteristics of carrier mediated Characteristics of carrier mediated

diffusion:diffusion: Down concentration GradientDown concentration Gradient Chemical Specificity:Chemical Specificity:

Carrier interact with specific molecule Carrier interact with specific molecule only.only.

Competitive inhibition:Competitive inhibition: Molecules with similar chemical Molecules with similar chemical

structures compete for carrier site.structures compete for carrier site. SaturationSaturation 饱和饱和 ::

VVmax max (transport maximum):(transport maximum): Carrier sites have become saturated.Carrier sites have become saturated.

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2.2 Facilitated diffusion through channels

Definition

Some transport proteins

have watery spaces all the way through the molecule

allow free movement of certain ions or molecules. They are called channel proteins.

Diffusion carried out by protein channel is termed channel mediated diffusion.

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Two important characteristics of the channels:

selectively permeable to specific substances

opened or closed by gates

Facilitated diffusion through channels

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Channel: aqueous 水的 pathways through the interstices 缝隙 of the protein molecules.

Each channel molecule is a protein complex.

through which the ions can diffuse across the membrane.

Facilitated diffusion through channels

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According to the factors that alter the conformational 构象 change of the protein channel, the channels are divided into 3 types:

Voltage gated channel

Chemically gated channel

Mechanically gated channel

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2. Facilitated Diffusion2. Facilitated Diffusion

2.1 2.1 Facilitated diffusion via carrierFacilitated diffusion via carrier 2.2 Facilitated diffusion through 2.2 Facilitated diffusion through

channelchannel 2.2.1 Voltage-gated ion channel2.2.1 Voltage-gated ion channel 2.2.2 Chemically-gated ion channel2.2.2 Chemically-gated ion channel 2.2.3 Mechanically-gated ion channel2.2.3 Mechanically-gated ion channel 2.2.4 Water channel2.2.4 Water channel

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2.2.1 Voltage-gated Channel

The molecular conformation of the gate responds to the electrical potential across the cell membrane

this type of channel is called voltage gate (or dependent) channel.

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Voltage-gated Na+ Channels Many flavors

nerves, glia 神经胶质 , heart, skeletal muscle

Primary role is action potential initiation

Multi-subunit 多亚基 channels (~300 kDa)

Skeletal Na+ Channel: 1 (260 kDa) and 1 (36kDa)

Nerve Na+ Channel: 112 (33 kDa)

gating/permeation machinery in 1 subunits

Three types of conformational states (close,

open or activation, inactivation) - each

controlled by membrane voltage

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2.2.2 Chemically-Gated Ion Channel

Some protein channel gates are opened by the binding of another molecule with the protein;

this causes a conformational change in the protein molecule that opens or closes the gate.

This is called chemical gating.

This type of channel is called chemically-gated (or dependent) channel

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Ligand 配合基 -Operated ACh Channels

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Ion channel runs through receptor. Receptor has 5

polypeptide subunits that enclose ion channel.

2 subunits contain ACh binding sites.

Ligand-Operated ACh Channels

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Channel opens when both sites bind to ACh.Permits diffusion of Na+

into and K+ out of postsynaptic 突触后 cell.

Inward flow of Na+ dominates .Produces EPSPs.

Ligand-Operated ACh Channels

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2.2.3 2.2.3 Mechanically-gated channelMechanically-gated channel

Some protein channel gates may be Some protein channel gates may be opened by the mechanical deformationopened by the mechanical deformation变形变形 of the cell membrane. of the cell membrane. mechanically-gated channel. mechanically-gated channel.

It plays a very important role in the It plays a very important role in the genesisgenesis 发生发生 of excitation of the hair cellsof excitation of the hair cells

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Organ of Corti

When sound waves move the basilar membrane it moves the hair cells that are connected to it,

but the tips of the hair cells are connected to the tectorial 顶盖membrane the hair cell get bent .

There are little mechanical gates on each hair cell that open when they are bent.

K+ goes into the cell and Depolarizes 去极化 the hair cell. (concentration of K+ in the endolymph 内淋巴 is very high)

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2.2.4 Water Channel

The structure of aquaporin

水通道

(AQP)

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Simple diffusion

Ion channel

Water channel

Water transportation through the membrane:

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Characteristics of the channelCharacteristics of the channel

High ionic selectivityHigh ionic selectivity Gating channelGating channel Functional states of channelFunctional states of channel Time dependenceTime dependence

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Short Review

2. Facilitated diffusion

2.1 Facilitated diffusion via carrier

2.2 Facilitated diffusion through channel

2.2.1 Voltage-gated ion channel

2.2.2 Chemically-gated ion channel

2.2.3 Mechanically-gated ion channel

2.2.4 Water channel

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3 Active transport3 Active transport When the cell membrane moves molecules or When the cell membrane moves molecules or

ions ions uphilluphill 费力费力 against a concentration against a concentration gradient gradient

(or uphill against an electrical or pressure (or uphill against an electrical or pressure gradient), gradient),

the process is called active transportthe process is called active transport 3.1 3.1 Primary active transportPrimary active transport 原发性原发性 3.2 Secondary active transport:3.2 Secondary active transport: 继发性 继发性