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.
