Understanding the functions of the organ systems requires profound knowledge of basic cellular mechanisms. Although each organ system differs in its overall function, all are undergirded by a common set of physiologic principles.
The following basic principles of physiology are introduced in this chapter: body fluids, with particular emphasis on the differences in composition of intracellular fluid and extracellular fluid; creation of these concentration differences by transport processes in cell membranes; the origin of the electrical potential difference across cell membranes, particularly in excitable cells such as nerve and muscle; generation of action potentials and their propagation in excitable cells; transmission of information between cells across synapses and the role of neurotransmitters; and the mechanisms that couple the action potentials to contraction in muscle cells.
These principles of cellular physiology constitute a set of recurring and interlocking themes. Once these principles are understood, they can be applied and integrated into the function of each organ system.
Water, a major component of the body, is distributed among two major compartments, ICF and ECF. ECF is further distributed among the plasma and the interstitial fluid. The differences in composition of ICF and ECF are created and maintained by transport proteins in the cell membranes.
Transport may be either passive or active. If transport occurs down an electrochemical gradient, it is passive and does not consume energy. If transport occurs against an electrochemical gradient, it is active. The energy for active transport may be primary (using ATP) or secondary (using energy from the Na+ gradient). Osmosis occurs when an impermeable solute creates an osmotic pressure difference across a membrane, which drives water flow.
Ion channels provide routes for charged solutes to move across cell membranes. The conductance of ion channels is controlled by gates, which are regulated by voltage or by ligands. Diffusion of a permeable ion down a concentration gradient creates a diffusion potential, which, at electrochemical equilibrium, is calculated by the Nernst equation. When several ions are permeable, each attempts to drive the membrane toward its equilibrium potential. Ions with the highest permeabilities make the greatest contribution to the resting membrane potential.
Action potentials in nerve and muscle consist of rapid depolarization (upstroke), followed by repolarization caused by the opening and closing of ion channels. Action potentials are propagated down nerve and muscle fibers by the spread of local currents, with the speed of conduction depending on the tissue’s cable properties. Conduction velocity is increased by increasing fiber size and by myelination.
Synapses between cells may be electrical or, more commonly, chemical. The prototype of the chemical synapse is the neuromuscular junction, which uses ACh as a neurotransmitter. ACh is released from presynaptic nerve terminals and diffuses across the synapse to cause depolarization of the motor end plate. Neurotransmitters at other synapses may be either excitatory (causing depolarization) or inhibitory (causing hyperpolarization).
In muscle, action potentials precede contraction. The mechanisms that translate the action potential into contraction are called excitation-contraction coupling. In both skeletal and smooth muscle, Ca2+ plays a central role in the coupling.
In skeletal muscle, the action potential is carried to the cell interior by the T tubules, where depolarization releases Ca2+ from terminal cisternae of the nearby sarcoplasmic reticulum. Ca2+ then binds to troponin C on the thin filaments, causing a conformational change, which removes the inhibition of myosin-binding sites. When actin and myosin bind, cross-bridge cycling begins, producing tension.
In smooth muscle, Ca2+ enters the cell during the action potential via voltage-gated Ca2+ channels. Ca2+ then binds to calmodulin, and the Ca2+-calmodulin complex activates myosin-light-chain kinase, which phosphorylates myosin. Myosin~P can bind actin, form cross-bridges, and generate tension. Other sources of intracellular Ca2+ in smooth muscle are ligand-gated Ca2+ channels in the sarcolemmal membrane and IP3-gated Ca2+ channels in the sarcoplasmic reticulum membrane.
Answer each question with a word, phrase, sentence, or numerical solution. When a list of possible answers is supplied with the question, one, more than one, or none of the choices may be correct. Correct answers are provided at the end of the book.
1 Solution A contains 100 mM NaCl, Solution B contains 10 mM NaCl, and the membrane separating them is permeable to Cl− but not Na+. What is the orientation of the potential difference that will be established across the membrane?
2 The osmolarity of a solution of 50 mmol/L CaCl2 is closest to the osmolarity of which of the following: 50 mmol/L NaCl, 100 mmol/L urea, 150 mmol/L NaCl, or 150 mmol/L urea?
3 How does the intracellular Na+ concentration change following inhibition of Na+-K+ ATPase?
4 Which phase of the nerve action potential is responsible for propagation of the action potential to neighboring sites?
5 How many quanta of acetylcholine (ACh) are required to depolarize the motor end plate from −80 mV to −70 mV if a miniature end plate potential (MEPP) is 0.4 mV?
6 A man is poisoned with curare. Which of the following agents would worsen his condition: neostigmine, nicotine, botulinus toxin, ACh?
7 Put these events in the correct temporal order: end plate potential (EPP), action potential in muscle fiber, ACh release from presynaptic terminal, MEPP, opening ligand-gated ion channels, opening Ca2+channels in presynaptic terminal, binding of ACh to nicotinic receptors, action potential in nerve fiber.
8 In skeletal muscle, at muscle lengths less than the length that generates maximum active tension, is active tension greater than, less than, or approximately equal to total tension?
9 Which of the following neurotransmitters would be inactivated by peptidases: ACh, Substance P, dopamine, glutamate, GABA, histamine, vasopressin, nitric oxide (NO)?
10 Solution A contains 10 mmol/L glucose, and Solution B contains 1 mmol/L glucose. If the glucose concentration in both solutions is doubled, by how much will the flux (flow) of glucose between the two solutions change (e.g., halve, remain unchanged, double, triple, quadruple)?
11 Adrenergic neurons synthesize which of the following: norepinephrine, epinephrine, ACh, dopamine, L-dopa, serotonin?
12 What effect would each of the following have on conduction velocity: increasing nerve diameter, increasing internal resistance (Ri), increasing membrane resistance (Rm), decreasing membrane capacitance (Cm), increasing length constant, increasing time constant?
13 How does hyperkalemia alter resting membrane potential (depolarizes, hyperpolarizes, or has no effect), and why does this cause muscle weakness?
14 During which of the following steps in cross-bridge cycling in skeletal muscle is ATP bound to myosin: rigor, conformational change in myosin that reduces its affinity for actin, power stroke?
15 Which of the following classes of drugs are contraindicated in a patient with myasthenia gravis: nicotinic receptor antagonist, inhibitor of choline reuptake, acetylcholinesterase (AChE) inhibitor, inhibitor of ACh release?
16 Solution A contains 100 mmol/L glucose and Solution B contains 50 mmol/L NaCl. Assume that gNaCl is 2.0, σglucose is 0.5, and σNaCl is 0.8. If a semipermeable membrane separates the two solutions, what is the direction of water flow across the membrane?
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