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This chapter discusses the diverging views of embryologists and geneticists about heredity and evolution. The two main reasons for this stemmed from research started in the 19th century. First, experimental embryologists were not concerned with adaptive changes to adult organisms. They were not concerned with the differences between individual varieties and species, but rather with the larger similarities and differences in the structural plans underlying different organismic types. They were interested in the form of the embryo and in the orderly changes during development — in how the parts of the organisms come together in space and time. Second, while geneticists and neo-Darwinian evolutionists maintained that changes in the nuclear chromosomal genes of eggs and sperm were the basis of evolution, many embryologists insisted that the cytoplasm of the egg played the primary role in heredity and development.

This chapter considers a major preoccupation of biology in the early part of the 20th century: the role of the cytoplasm, particularly in development. It discusses studies of Paramecium and other ciliates, the Paramecium life cycle, the Paramecium mating problem, and the model status of Paramecium.

This chapter deals with the regulatory effects of internally added Ca²⁺ and Mg²⁺ on the Na⁺ and K⁺ channel activities of an excitable membrane. The regulatory effects of internally applied Ca²⁺ and Mg²⁺ ions, using intracellularly perfused squid axons, is discussed. It has previously beeen shown using squid giant axons that the action of internal Ca²⁺ on Na⁺ channel activity causes deterioration, or little effect. The internally added Ca²⁺ produces a Na⁺ action potential without any electrical stimulation in squid axons. Low concentrations of Ca²⁺ and Mg²⁺ exist in the cytoplasm of animal cells. Changes in concentration of Ca²⁺ are closely related to several functions, including membrane processes such as excitability and synaptic transmission. The internally applied Ca²⁺ and Mg²⁺ commonly have two types of effect on ion channel activities. First, they cause a lowering of the threshold voltage level for Na⁺ and K⁺ channel activation. The lowering of threshold potential caused by Ca²⁺ and Mg²⁺ is a notable and important effect which suggests that the membrane becomes more excitable in the presence of increased levels of intracellular divalent cations. Second, the internally applied Ca²⁺ and Mg²⁺ reduce Na⁺ and K⁺ currents by a concentration-dependent amount that differs for internally applied Ca²⁺ and Mg²⁺ respectively. The similarities and differences between Ca²⁺ and Mg²⁺ effects on ion channel activities are also described.

Radiofrequency dielectric properties of cell suspensions provide rich information on the structural and electrical properties of cells. Cell suspensions show α-and β-dispersions, which usually appear below and above 10 kHz, respectively. For the β-dispersion, the theoretical models of cells presented in Chapter 1.2 are overviewed, in order to illustrate their relevance and appropriateness to various types of cells. Next, the chapter considers problems in estimating the electrical parameters of the cell components including the plasma membrane and the cytoplasm from the β-dispersion. At the end this chapter discusses the membrane properties and conditions (i.e., surface charges, membrane folding, membrane disruption, and mobile charges in the membrane) that provide possible polarization mechanisms responsible for the α-dispersion.

Previous chapters present the characteristics of drug movement through the body. Diffusion is an essential mode of transport at the microscopic scale; concentration gradients drive a substantial fraction of the molecular movements within cells and the extracellular space. The confinement and regulated passage of molecules within compartments of a tissue or cell is also essential for function; membranes confine molecules to spatial locations and regulate transport between these isolated spaces (Chapter 5). Membranes frequently are the major obstacles to the entry or distribution of therapeutic compounds (Chapter 7). Therefore, much of the effort in drug design and drug delivery is devoted to overcoming these diffusional or membrane barriers. This chapter describes strategies for manipulating agents in order to increase their biological activity. The sections orbit a central assumption: i.e., agents can be modified to make analogous agents (analogs), which are chemically distinct from the original compound, but produce a similar biological effect. Nature uses a similar strategy, called “biotransformation” to assure elimination of many toxic compounds and drugs. Substantial chemical modification is often needed in order to impact physical properties that influence drug distribution such as stability or solubility; the challenge of drug modification is to identify chemical features that can be changed without sacrificing biological activity. Often, our understanding of the relationship between chemical structure and biological function for an agent is incomplete, making the rational production of analogs difficult. Drug modifications are frequently directed at altering properties that influence the concentration of the compound (i.e., its solubility), the duration of action (which is usually related to its stability in tissue), or the ability of drug molecules to move between compartments in tissues (which is often related to its permeability in membranes). A chemical modification can effect multiple properties, so these divisions are frequently not as distinct as the section headings suggest. Many agents are protected from degradation within tissues by binding. Binding provides a mechanism for sequestering an unstable or potent compound within a region of a tissue. Protective binding occurs frequently within the plasma and extracellular matrix (ECM); the complex molecular composition of these tissues provides many potential binding sites.

As noted earlier and as anticipated by Charles and Francis Darwin it has been argued that plants sense the direction of gravity (gravitropism) by movement of starch granules found in cells called statocytes that contain compartments (organelles) called statoliths. The synthesis of statoliths appears to occur in the plastid (plant organelle) compartments called amyloplasts (Figure 7.1, 1). It has been suggested that this gravitropic signal then leads to movement of plant hormones such as indole-3-acetic acid (auxin) (Figure 7.2), through the phloem opposite to the pull of gravity to promote stem growth. Chloroplasts (Figure 7.1, 2) are cell compartments (plastids or organelles) in which photosynthesis is carried out. The process of photosynthesis, discussed more fully later, is accompanied by the production of adenosine triphosphate (ATP) from adenosine diphosphate (ADP) and inorganic phosphate (Pi) (Figure 7.3). ATP is consumed and converted to ADP and Pi in living systems. The cycle of production and consumption allows ATP to serve as an “energy currency” to pay for the reactions in living systems. Beyond this generally recognized critical function of chloroplasts, it has recently been pointed out that light/dark conditions affect alternative splicing of genes which may be necessary for proper plant responses to varying light conditions. The organelles or plastids which contain the pigments for photosynthesis and the amyloplasts that store starch are only two of many kinds of plastids. Other plastids, leucoplasts for example, hold the enzymes for the synthesis of terpenes, and elaioplasts store fatty acids. Apparently, all plastids are derived from proplastids which are present in the pluripotent apical and root meristem cells. The cell wall (Figure 7.1, 3) is the tough, rigid layer that surrounds cells. It is located on the outside of the flexible cell membrane, thus adding fixed structure. A representation of a portion of the cell wall (as made up of cellulose and peptide cross-linking) is shown below in Figure 7.7. The cells will have different sizes as a function of where they are found (e.g., leaf, stalk, root), but in every case, the cell wall limits the size of the membrane that lies within.