Harpers

428 / CHAPTER 41INSIDEATPADP+P i3 Na +Mg 2+Membrane2 K + 2 K +OUTSIDE3 Na +Figure 41–13. Stoichiometry of the Na + -K + ATPasepump. This pump moves three Na + ions from inside thecell to the outside and brings two K + ions from the outsideto the inside for every molecule of ATP hydrolyzedto ADP by the membrane-associated ATPase. Ouabainand other cardiac glycosides inhibit this pump by actingon the extracellular surface of the membrane.(Courtesy of R Post.)membrane protein and requires phospholipids for activity.The ATPase has catalytic centers for both ATPand Na + on the cytoplasmic side of the membrane, butthe K + binding site is located on the extracellular side ofthe membrane. Ouabain or digitalis inhibits this ATPaseby binding to the extracellular domain. Inhibitionof the ATPase by ouabain can be antagonized by extracellularK + .Nerve Impulses Are TransmittedUp & Down MembranesThe membrane forming the surface of neuronal cellsmaintains an asymmetry of inside-outside voltage (electricalpotential) and is electrically excitable. When appropriatelystimulated by a chemical signal mediated bya specific synaptic membrane receptor (see discussion ofthe transmission of biochemical signals, below), gates inthe membrane are opened to allow the rapid influx ofNa + or Ca 2+ (with or without the efflux of K + ), so thatthe voltage difference rapidly collapses and that segmentof the membrane is depolarized. However, as a resultof the action of the ion pumps in the membrane,the gradient is quickly restored.When large areas of the membrane are depolarizedin this manner, the electrochemical disturbance propagatesin wave-like form down the membrane, generatinga nerve impulse. Myelin sheets, formed bySchwann cells, wrap around nerve fibers and provide anelectrical insulator that surrounds most of the nerve andgreatly speeds up the propagation of the wave (signal)by allowing ions to flow in and out of the membraneonly where the membrane is free of the insulation. Themyelin membrane is composed of phospholipids, cholesterol,proteins, and GSLs. Relatively few proteins arefound in the myelin membrane; those present appear tohold together multiple membrane bilayers to form thehydrophobic insulating structure that is impermeableto ions and water. Certain diseases, eg, multiple sclerosisand the Guillain-Barré syndrome, are characterizedby demyelination and impaired nerve conduction.Glucose Transport InvolvesSeveral MechanismsA discussion of the transport of glucose summarizesmany of the points made in this chapter. Glucose mustenter cells as the first step in energy utilization. Inadipocytes and muscle, glucose enters by a specifictransport system that is enhanced by insulin. Changesin transport are primarily due to alterations of V max(presumably from more or fewer active transporters),but changes in K m may also be involved. Glucose transportinvolves different aspects of the principles of transportdiscussed above. Glucose and Na + bind to differentsites on the glucose transporter. Na + moves into the celldown its electrochemical gradient and “drags” glucosewith it (Figure 41–14). Therefore, the greater the Na +gradient, the more glucose enters; and if Na + in extracellularfluid is low, glucose transport stops. To maintaina steep Na + gradient, this Na + -glucose symport isdependent on gradients generated by an Na + -K + pumpthat maintains a low intracellular Na + concentration.Similar mechanisms are used to transport other sugarsas well as amino acids.The transcellular movement of sugars involves oneadditional component: a uniport that allows the glucoseaccumulated within the cell to move across a differentsurface toward a new equilibrium; this occurs in intestinaland renal cells, for example.Cells Transport Certain MacromoleculesAcross the Plasma MembraneThe process by which cells take up large molecules iscalled “endocytosis.” Some of these molecules (eg,polysaccharides, proteins, and polynucleotides), whenhydrolyzed inside the cell, yield nutrients. Endocytosisprovides a mechanism for regulating the content of certainmembrane components, hormone receptors beinga case in point. Endocytosis can be used to learn moreabout how cells function. DNA from one cell type canbe used to transfect a different cell and alter the latter’sfunction or phenotype. A specific gene is often employedin these experiments, and this provides a uniqueway to study and analyze the regulation of that gene.DNA transfection depends upon endocytosis; endocy-