第二章 细胞的基本功能

【目的要求】了解细胞膜和骨骼肌的基本结构，细胞的信号转导，局部电位及特征。熟悉动作电位的传导，横纹肌细胞收缩的机制，影响横纹肌收缩效能的因素。掌握细胞膜的物质转运功能，细胞的静息电位及动作电位的概念及产生机制，组织的兴奋和兴奋性，阈刺激和阈电位的概念，神经-肌接头处兴奋的传递，兴奋-收缩耦联，等张收缩和等长收缩的概念。

【教学内容】

1．  细胞膜的结构概述，物质跨膜转运方式的分类、各转运方式的特点，钠泵的生理功能，信号转导功能。

2． 离子通道型受体、G蛋白耦联受体、酶联型受体和核受体介导的信号转导。

3．  细胞的生物电现象，静息电位的概念及产生机制，动作电位的概念、产生机制和特点，动作电位的触发及阈电位，动作电位的传导，可兴奋组织、兴奋和兴奋性，刺激、阈值（阈强度）和阈刺激。电紧张电位和局部电位，

4．  神经-肌接头处兴奋的传递过程、特征及影响因素，骨骼肌细胞的微细结构，横纹肌细胞收缩机制，兴奋-收缩耦联，等张收缩和等长收缩，影响横纹肌收缩效能的因素。

【计划学时】8学时。

Chapter II Basic Functions of Cell

Transport across Cell Membrane

The cell membrane plays an active role in maintaining the compositional differences between the extracellular and intracellular fluids. It does this by controlling the transport of ions and other substances through the membrane. There are passive and active mechanisms by which substance pass through membranes.

  Passive transport Metabolic energy is not required for this process. Simple diffusion is the movement of molecules from one location to another by random thermal motion. The net flux between two compartments always proceeds from higher to lower concentration of the diffusing substance. The magnitude of the net flux across a plasma membrane is directly proportional to the concentration difference across the membrane, the surface area of the membrane, and the membrane permeability constant. Nonpolar molecules diffuse through the lipid portions of membranes much more rapidly than polar or ionized molecules because nonpolar molecules can dissolve in the nonpolar lipids. Mineral ions diffuse across membranes by passing through ion channels formed by integral membrane proteins. The net diffusion of ions across a membrane depends on the concentration gradient and the membrane potential. The flux of ions across a membrane can be altered by opening or closing ion channels.

Facilitated diffusion is a carrier-mediated transport process that moves molecules from higher to lower concentration across a membrane until the two concentrations become equal. The mediated transport of molecules across a membrane involves the binding of the transported solute to a carrier protein in the membrane. Changes in the conformation of the carrier protein move the binding site to the opposite side of the membrane, where the solute dissociates from the carrier protein. The binding sites on carrier proteins exhibit chemical specificity and saturation.

   Active transport Active transport is a carrier-mediated-transport process that moves molecules against an electrochemical difference across a membrane and requires an input of energy. Primary active transport carriers use the phosphorylation of the carrier by ATP to produce the change in binding-site affinity. Secondary active transport carriers use the binding of ions (often Na) to the carrier to produce the change in binding-site affinity. In secondary active transport the downhill flow of an ion, often Na, into the cell is linked either to movement of a second solute from lower extracellular to higher intracellular concentration (cotransport) or to solute movement from lower intracellular concentration to higher extracellular concentration (countertransport).

    The most important active transport mechanism of all cells is the sodium-potassium pump, which pumps Na out of the cell and K into the cell. It is this pump that maintains the low Na concentration and high K concentration in the intracellular fluid.

  Endocytosis and exocytosis During endocytosis, regions of the plasma membrane invaginate and pinch off to form vesicles that enclose a small volume of extracellular material. In most cells, endocytotic vesicles fuse with the membranes of lysosomes, in which the vesicle contents are digested by lysosomal enzymes. Exocytosis, which occurs when intracellular vesicles fuse with the plasma membrane, provides a way to insert new segments of membrane into the plasma membrane, and provides a route by which membrane-impermeable molecules synthesized by cells can be released into the extracellular fluid. 

Signal Transduction Mechanisms for Plasma Membrane Receptors

Intercellular communication is essential to the various reflexes and local responses and is achieved by neurotransmitters, hormones, and other factors. Receptors for chemical messengers are proteins located either inside the cell or, much more commonly, in the plasma membrane. The binding of a messenger by a receptor manifests specificity，saturation ,and competition . Binding a chemical messenger activates a receptor, and this initiates one or more signal transduction pathways leading to the cell's response. The receptor may activate, via a Gs protein, or inhibit, via a Gi protein, the membrane enzyme adenylate cyclase, which catalyzes the conversion of cytosolic ATP to cyclic AMP. Cyclic AMP acts as a second messenger to activate intracellular cAMP-dependent protein kinases. These protein kinases phosphorylate proteins that mediate the cell's ultimate responses to the first messenger. Cyclic GMP formed by the action of membrane guanylate cyclase, also functions as a second messenger through a protein kinase.

  The calcium ion is one of the most widespread second messengers, and an activated receptor can increase cytosolic calcium concentration in several ways. The receptor may open a membrane calcium channel, which allows extracellular calcium to diffuse into the cell. The receptor may activate the membrane enzyme phospholipase C, which breaks down phosphatidylinositol bisphosphate (PIP2) into two-second messengers inositol trisphosphate (IP3) and diacylglycerol (DAG). IP3 stimulates the release of calcium from the cell's endoplasmic reticulum. Calcium binds to one of several intracellular proteins, most often calmodulin. Calcium-activated calmodulin activates or inhibits many proteins, including calmodulin-dependent protein kinases. DAG activates protein kinase C, which phosphorylates many proteins. The receptor can itself act as a protein kinase termed as tyrosine kinase. A single messenger may have multiple receptors, each triggering a different response. The various signal transduction mechanisms and second messenger often function together.

Bioelectric Phenomena of Cell

    Resting potential At rest, the membrane is mainly permeable to K and relatively impermeable to other kinds of ions. The K diffuse outward down the concentration gradient until their movement is balanced by the electrical gradient which is the equilibrium potential of K. In most tissues, the values of resting potential and equilibrium potential of K are very close.

   Action potentials An action potential is initiated when a depolarizing stimulus opens enough voltage-gated Na+ channels that the Na+ conductance exceeds the K+ conductance, setting up a positive-feedback cycle in which depolarization rapidly opens the remaining Na+ channels. Repolarization is the result of two factors: spontaneous inactivation of Na+ channels and the opening of K+ channels. These two factors make the membrane absolutely refractory to a second stimulus for a few milliseconds after an action potential is initiated. When a sufficient number of inactivated Na+ channels have reverted to the closed but potentially responsive state, the membrane is still relatively refractory until the K+ channels have closed.

  The velocity of conduction of an action potential down an axon is determined by the diameter of the fiber and is also greatly increased by myelination in the case of axons. In myelinated axons, conduction is saltatory: In a nerve trunk containing many axons, stimulation evokes many simultaneous action potentials that propagate in both directions from the site of stimulation and whose currents can be recorded as a compound action potential.

Excitation Transmission of Neuromuscular Junction

The axon of a motor neuron forms a neuromuscular junction with many muscle fibers in a muscle. Each muscle fiber is innervated by only one motor neuron. A motor unit consists of a single motor neuron and the fibers it innervates. Acetylcholine released by an action potential in a motor neuron binds to receptors on the motor end plate of the muscle membrane, opening ion channels that allow the passage of sodium and potassium ions, and depolarizing the end-plate membrane, then depolarizing the skeletal muscle cell membrane. A single action potential in a motor neuron is sufficient to produce a single action potential in a skeletal muscle fiber.

Structure and Contractile Mechanisms of Muscle Cell

Three types of muscle, i.e., skeletal, smooth, and cardiac, are found in the body. Skeletal muscle is attached to bones and moves and supports the skeleton. Smooth muscle surrounds hollow cavities and tubes. Cardiac muscle is the muscle of the heart (to see Circulation system).

Contraction of the muscle is triggered when a muscle action potential causes the release of Ca++ from the terminal cisternae of the sarcoplasmic reticulum in a process referred to as excitation-contraction coupling. In a resting muscle, attachment of cross bridges to actin is prevented by rod-shaped tropomyosin molecules that lie on the actin filaments and block the myosin binding sites on actin. Contraction is initiated by an increase in cytosolic calcium concentration. The calcium ions bind to troponin, producing a change in its shape that moves tropomyosin out of its blocking position, allowing cross bridges to bind to actin. Relaxation of a contracting muscle fiber is achieved by actively transporting the cytosolic calcium ions back into the sarcoplasmic reticulum.

Mechanics of Muscle Contraction

Two types of contractions can occur following activation of a muscle fiber: an isometric contraction-the muscle generates tension but does not change length; an isotonic contraction-the muscle shortens but the tension is constant, moving a load. Increasing the frequency of action potentials in a muscle fiber increases the mechanical response (tension or shortening), up to the level of maximal tetanic tension. Maximum isometric tetanic tension is produced when there is a maximal overlap of thick and thin filaments, that is, at the optimal length. Stretching a fiber beyond its optimal length decreases the filament overlap and decreases the tension produced, while decreasing the fiber length below optimal length also decreases the tension generated due to interference with cross-bridge binding. The velocity of muscle fiber shortening decreases with increases in load. Maximum velocity occurs at zero load.

Smooth Muscle

The thick and thin filaments of smooth muscle are not organized into sarcomeres but form a network that is able to develop force over a broad operating range. Contraction in smooth muscle is controlled by a second messenger system in which the primary step is Ca++ entry. Ca++ binds to calmodulin and also to myosin. The Ca++-calmodulin complex activates myosin light-chain kinase, which phosphorylates myosin, causing it to form crossbridges that cycle. In smooth muscle, tension can be maintained with little expenditure of ATP.

内容提要

（一）细胞膜的基本结构——液态镶嵌模型

该模型的基本内容：以液态脂质双分子层为基架，其中镶嵌着具有不同生理功能的蛋白质分子，并连有一些寡糖和多糖链。

（二）细胞膜物质转运功能

物质进出细胞必须通过细胞膜，细胞膜的特殊结构决定了不同物质通过细胞的难易。物质通过细胞膜的转运有以下几种形式：

1．被动转运：包括单纯扩散和易化扩散两种形式。

（1）单纯扩散：是指小分子脂溶性物质由高浓度的一侧通过细胞膜向低浓度的一侧转运的过程。跨膜扩散的最取决于膜两侧的物质浓度梯度和膜对该物质的通透性。单纯扩散在物质转运的当时是不耗能的，其能量来自高浓度本身包含的势能。O₂、CO₂、NH₃等气体分子及尿素等以这种方式跨膜转运。  

（2）易化扩散：指非脂溶性小分子物质在特殊膜蛋白的协助下，由高浓度的一侧通过细胞膜向低浓度的一侧移动的过程。参与易化扩散的膜蛋白有载体蛋白质和通道蛋白质。

以载体为中介的易化扩散特点如下：（1）竞争性抑制；（2）饱和现象；（3）结构特异性。

以通道为中介的易化扩散特点如下：（1）相对特异性；（2）无饱和现象；（3）通道有“开放”和“关闭”两种不同的机能状态。

体液中的离子物质是通过通道转运的，而一些有机小分子物质，例如葡萄糖、氨基酸等则依赖载体转运。

2．主动转运，包括原发性主动转运和继发性主动转运。

主动转运是指细胞消耗能量将物质由膜的低浓度一侧向高浓度的一侧转运的过程。主动转运的特点是：（1）在物质转运过程中，细胞要消耗能量；（2）物质转运是逆电-化学梯度进行；（3）转运的为小分子物质；（4）原发性主动转运主要是通过离子泵转运离子，继发性主动转运是指依赖离子泵转运而储备的势能从而完成其他物质的逆浓度的跨膜转运。

最常见的离子泵转运为细胞膜上的钠泵（Na⁺-K⁺泵）。

3．出胞和入胞作用。（均为耗能过程）

出胞是指某些大分子物质或物质团块由细胞排出的过程，主要见于细胞的分泌活动。入胞则指细胞外的某些物质团块进入细胞的过程。内分泌细胞分泌激素、神经细胞分泌递质属于出胞作用；上皮细胞、免疫细胞吞噬异物属于入胞作用。

（三）细胞的生物电现象

生物电的表现形式： 静息电位、动作电位、局部电位。

1.静息电位：细胞处于安静状态下（未受刺激时）膜内外的电位差。

静息电位表现为膜外相对为正而膜内相对为负。

（1）形成机制：

①安静时细胞膜两侧存在离子浓度差（离子不均匀分布）。

②安静时细胞膜主要对K⁺通透。也就是说，细胞未受刺激时，膜上离子通道中主要是K⁺通道开放，允许K⁺由细胞内流向细胞外，而不允许Na⁺、Ca²⁺由细胞外流入细胞内。

K⁺外流的平衡电位即静息电位。

（2）特征：静息电位是K⁺外流形成的膜两侧稳定的电位差。

只要细胞未受刺激、生理条件不变，这种电位差持续存在，而动作电位则是一种变化电位。细胞处于静息电位时，膜内电位较膜外电位为负，这种膜内为负，膜外为正的状态称为极化状态。而膜内负电位减少或增大，分别称为去极化和超级化。细胞先发生去极化，再向安静时的极化状态恢复称为复极化。

2.动作电位：

（1）概念：可兴奋组织或细胞受到阈上刺激时，在静息电位基础上发生的快速、可逆转、可传播的细胞膜两侧的电变化。动作电位的主要成份是峰电位。

（2）形成机制：

形成条件：①细胞膜两侧存在离子浓度差，细胞膜内K⁺浓度高于细胞膜外，而细胞外Na⁺、Ca²⁺、Cl^-高于细胞内，这种浓度差的维持依靠离子泵的主动转运。（主要是Na⁺-K⁺泵的转运）。

②细胞膜在不同状态下对不同离子的通透性不同，例如，安静时主要允许K⁺通透，而去极化到阈电位水平时又主要允许Na⁺通透。

③可兴奋组织或细胞受阈上刺激。

形成过程：阈（或阈上）刺激→细胞膜部分去极化→Na⁺少量内流→去极化至阈电位水平→Na⁺内流与去极化形成正反馈（Na⁺爆发性内流）→达到Na⁺平衡电位（膜内为正膜外为负）→形成动作电位上升支。

膜去极化达一定电位水平→Na⁺内流停止、K⁺迅速外流→形成动作电位下降支。

阻断Na⁺通道（河豚毒）能阻碍动作电位的产生。

（3）动作电位特征： “全或无”式的。

①动作电位的形态、幅度和时间不随刺激强度的变化而变化

②动作电位的幅度不因传导距离增加而减小(不衰减性传导)。

（4）兴奋在同一细胞上的传导：可兴奋细胞兴奋的标志是产生动作电位，因此兴奋的传导实质上是动作电位向周围的传播。动作电位以局部电流的方式传导，直径大的细胞电阻较小传导的速度快。有髓鞘的神经纤维动作电位以跳跃式传导，因而比无髓纤维传导快。

（5）一次兴奋后细胞兴奋性的周期性变化：绝对不应期——相对不应期——超常期——低常期——恢复。

3.局部电位：

（1）概念：细胞受到阈下刺激时，细胞膜两侧产生的微弱电变化（较小的膜去极化或超极化反应）。或者说是细胞受刺激后去极化未达到阈电位的电位变化。

（2）形成机制：阈下刺激使膜通道部分开放，产生少量去极化或超极化，故局部电位可以是去极化电位，也可以是超极化电位。局部电位在不同细胞上由不同离子流动形成，而且离子是顺着浓度差流动，不消耗能量。

（3）特点： ①不是“全或无”式。指局部电位的幅度与刺激强度正相关，而与膜两侧离子浓度差无关②可以总和。局部电位没有不应期，一次阈下刺激引起一个局部反应虽然不能引发动作电位，但多个阈下刺激引起的多个局部反应如果在时间上（多个刺激在同一部位连续给予）或空间上（多个刺激在相邻部位同时给予）叠加起来（分别称为时间总和或空间总和），就有可能导致膜去极化到阈电位，从而爆发动作电位。 ③电紧张扩布。局部电位不能像动作电位向远处传播，只能以电紧张的方式，影响附近膜的电位。电紧张扩布随扩布距离增加而衰减。

（四）神经肌肉接头处的信息传递过程

神经末梢兴奋（接头前膜）发生去极化→膜对Ca²⁺通透性增加→Ca²⁺内流→神经末梢释放递质ACh→ACh通过接头间隙扩散到接头后膜（终板膜）并与N型受体结合→终板膜对Na⁺、K⁺（以Na⁺为主）通透性增高→Na⁺内流→终板电位→总和达阈电位→肌细胞产生动作电位。

特点：①单向传递；②传递延搁；③易受环境因素影响。

总结：①神经肌肉接头处的信息传递实际上是“电—化学—电”的过程。 ②终板电位是局部电位，具有局部电位的所有特征，本身不能引起肌肉收缩；但每次神经冲动引起的ACh释放量足以使产生的终板电位总和达到邻近肌细胞膜的阈电位水平，使肌细胞产生动作电位。因此，这种兴奋传递是一对一的。③在接头前膜无Ca²⁺内流的情况下，ACh有少量自发释放，这是神经紧张性作用的基础。

（五）肌细胞的收缩功能

1.骨骼肌的特殊结构：

肌纤维内含大量肌原纤维和肌管系统，肌原纤维由肌小节构成，粗、细肌丝构成的肌小节是肌肉进行收缩和舒张的基本功能单位。肌管系统包括肌原纤维去向一致的纵管系统和与肌原纤维垂直去向的横管系统。纵管系统的两端膨大成含有大量Ca²⁺的终末池，一条横管和两侧的终末池构成三联管结构，它是兴奋收缩耦联的关键部位。

2.粗、细肌丝蛋白质组成：

（1）粗肌丝由肌凝蛋白（肌球蛋白）组成。

横桥：具ATP酶活性，可与细肌丝上横桥结合位点结合。

（2）细肌丝由肌动蛋白（肌纤蛋白）、原肌凝蛋白（原肌球蛋白）和肌钙蛋白组成。

3.兴奋收缩耦联过程：

（1）电兴奋通过横管系统传向肌细胞深处。

（2）三联管的信息传递。

（3）纵管系统对Ca²⁺的贮存、释放和再聚积。

4.肌肉收缩过程：

肌细胞膜兴奋传导到终池→终池Ca²⁺释放→肌浆Ca²⁺浓度增高→Ca²⁺与肌钙蛋白结合→原肌凝蛋白变构→肌球蛋白横桥头与肌动蛋白结合→横桥头ATP酶激活分解ATP→横桥扭动→细肌丝向粗肌丝滑行→肌小节缩短。

5.肌肉舒张过程：与收缩过程相反。

由于舒张时肌浆内钙的回收需要钙泵作用，因此肌肉舒张和收缩一样是耗能的主动过程。

（六）肌肉收缩的外部表现和力学分析

1.骨骼肌收缩形式：

（1）等长收缩和等张收缩

等长收缩：张力增加而无长度缩短的收缩，例如人站立时对抗重力的肌肉收缩是等长收缩，这种收缩不做功。

等张收缩：肌肉的收缩只是长度的缩短而张力保持不变。可使物体产生位移，因此可以做功。

整体情况下常是等长、等张都有的混合形式的收缩。

（2）单收缩和复合收缩

由于不应期的存在动作电位不会发生叠加，只能单独存在。肌肉发生复合收缩时，出现了收缩形式的复合，但引起收缩的动作电位仍是独立存在的。

随着兴奋频率的增高，骨骼肌的收缩形式可由单收缩变为不完全强直收缩直到完全强直收缩。 强直收缩是在上一次收缩的基础上收缩，因此比单收缩效率高，整体情况下的收缩通常都是完全强直收缩。 

2.影响骨骼肌收缩的主要因素：

（1）前负荷：在最适前负荷时产生最大张力，达到最适前负荷后再增加负荷或增加初长度，肌肉收缩力降低。

（2）后负荷：是肌肉开始缩短后所遇到的负荷。

后负荷与肌肉缩短速度呈反变关系。

（3）肌肉收缩力：即肌肉内部机能状态。

钙离子、肾上腺素、咖啡因提高肌肉收缩力。

缺氧、酸中毒、低血糖等降低肌肉的收缩力。