Chapter2

　This chapter describes the basic features of all kinds of tissue cells, an important foundation for understanding physiology. These features include: 1. the structure of cell membrane and transport of substances through cell membrane; 2. electrical phenomena of the cells; 3.signal transduction; 4. muscular contraction.
A mammalian cell membrane is composed of two layers of lipid in which protein molecules are embedded. The lipid composition of the cell membrane acts as a barrier, which limits transmembrane movement for most of the molecules inside and outside of the cell. Some of the proteins in the cell membrane, however, form structures that permit transmembrane movement for certain water-soluble molecules.
The cell membrane is therefore described as semipermeable, through which different kinds of substances pass across in different ways. Lipid-soluble molecules are capable of moving freely across the cell membrane by simple diffusion down their concentration gradients. Most of the molecules inside and outside of cells, however, cannot cross membrane without assistance. Two kinds of proteins in the cell membrane, called channels and carriers, provide permeability for these water-soluble substances, through which ions and glucose amino acid can pass across membrane. Those two kinds of transmembrane movement are called facilitated diffusion. In some situations, the molecules pass though the membrane against a concentration gradient and this process is called active transport. The energy derived from ATP is necessary for this process, and the protein involved in active transport named pump. If the molecules are bigger, they cannot cross the membrane through the channel or carrier, and those substances get into or out of the cell through even more complicated mechanisms called endocytosis and exocytosis, respectively..
　Signal transduction refers to the processes by which intercellular messengers (such as neurotransmitters, hormones, neurotrophic factors and cytokines) which bind to specific receptors on or in the target cell, are converted into biochemical and or electrical signals within that cell. In turn, such signals can modify cellular function in different ways. Four general patterns of signal transduction occur in almost all mammalian cells. One pattern involves receptors on the cell surface which are coupled with guanine nucleotide-binding proteins or G proteins on the inner face of the membrane. Binding of ligands to these receptors initiates receptor-G protein interactions that produce a range of biological effects on target cells. The main effect is to trigger complex cascades of intracellular messengers that lead to the generation of second messengers and the regulation of protein phosphorylation, and ultimately to diverse physiologic responses to extracellular stimuli. Protein phosphorylation seems the final common pathway in the regulation of cellular function. A second pattern of signal transduction again involves cell surface receptors and is characterized by direct activation of a class of protein kinase called tyrosine protein kinase. Binding of ligands to these receptors triggers cascades of further phosphorylation and leads to activation MAPK, which is involved in regulation of the process of gene expression. A third pattern of signal transduction is mediated by ligand-gated ion channels or receptor ionophores in the plasma membrane. In response to the binding of transmitters, the receptor undergoes a conformational change, opening the gate and allowing ions to diffuse along their concentration gradient and lead to the change of membrane potential of the target cell. A fourth pattern is characterized by activation receptors that are located inside the cell. After binding to the intercellular messenger, typically a hormone, these receptors are translocated to the nucleus, where they bind DNA and function as transcription factors to regulate the gene expression.
　The plasma membranes of all excitable cells exhibit a small difference in electrical charge between the inside and the outside of the cell called the membrane potential and this can change between the resting potential and the action potential. In the resting state and without stimulation, cells maintain a negative electrical potential inside in relative to the outside. Two characteristics of cells contribute to their ability to maintain this electrical potential. First, the cell membrane is differentially permeable to ions, in the resting state all cells are highly permeable to K+, and relatively impermeable to other ions. Second, different types of ions are unequally distributed across the cell membrane. Generally, there are higher concentrations of K+ and P- and lower concentrations of Na+ and Cl- inside of the cell than there are outside. In the resting state, K+ flows down its concentration gradient from the inside to the outside of the cell. Positive charges in this way accumulate outside of the cell membrane and because the P- cannot cross the membrane in company with the K+, an electrical potential develops across the membrane. The net movement of K+ between inside and outside of the cell membrane stops when the electrical force repelling further flow of K+ out of the cell equals to the force of the concentration gradient. At this point K+ has reached its equilibrium potential (Ek), which can be estimated with the Nernst equation. The action potential is a rapid depolarisation of the membrane potential, which can be propagated over the surface of the cell. At the peak of action potential, the membrane potential becomes positive, quite close to the equilibrium potential for ENa. Before generation of the action potential, membrane potential must first decreases (depolarize) to reach a special value called the threshold potential, at which the permeability of Na+ increases rapidly and in turn triggers the action potential. However, the increase of the Na+ conductance lasts only a short time (1-2ms), and K+ channels open more slowly to repolarise the membrane.. Both these factors contribute to the process of the returning the membrane potential to its resting value. All action potentials (or spikes) in a given cell are the same size regardless of their amplitude of stimulus and this phenomena is called the all-or-none rule. During the time course of a spike, the cell becomes completely inexcitable, or refractory, meaning that the cell will not fire again no matter how large the stimulus.
　Muscles can be divided into two groups, striated and smooth, based on their appearance under light microscope. Striated muscle is characterized by the regular striations seen under the microscope and includes skeletal muscles that are responsible for body movement and cardiac muscles that are responsible for the pumping action of the heart. Muscle cells consist of bundless of still smaller fibres called myofibrils. Under the electron microscope, myofibrils can be seen to consist of two kinds of longitudinally oriented filaments called thick and thin filaments. The thick filaments are aggregates of a protein called myosin and contain ATP splitting enzyme activity (ATPase) in a cross-bridge which swings out from the thick filament.. The thin filaments are largely made up of the protein actin. The basic unit of contraction of muscle is sarcomere and it is a special structure between two Z lines. The excitation of a muscle cell results from excitatory transmission through a nerve-muscle junction leading to the generation of an action potential of the muscle cell. This action potential initiates contraction of the cell by the process of excitation-contraction coupling, in which the elevation of Ca2+ is the critical factor to trigger muscle contraction. In the process of contraction, neither the thick or thin filaments change in their length. Rather, shortening occurs because the thick filaments pull the thin filaments past them. These thin filaments slide between thick filaments towards the middle line of the sarcomere. Force developed during the contraction is due to the interaction of thick and thin filaments and can be affected by different factors, including initial length, which is the length before muscle contraction. The maximum force can be produced if the muscle reaches a special length called optimal initial length before contraction. The mechanism underlying this phenomena is the maximum overlap between the thick and thin filaments allowing interaction by all cross-bridges and ultimately leading to the creation of maximum force.