Proteins and other organic molecules bind to *Ca++ and Pi(H2PO4−/HPO4−2), resulting in their total concentration in the plasma being 1.0-1.4 mmol/L and ionized concentration being 0.5-0.7 mmol/L. Cells also sequester large amounts of Ca++ and contain significant Pi concentrations within organic molecules like adenosine triphosphate (ATP).

The maintenance of intracellular ionic composition and cell volume is achieved through specific transporters in the plasma membrane. This section provides an overview of the mechanisms involved in regulating the intracellular ionic environment, membrane potential, and cellular volume.

The specific composition of ions within cells varies among different tissues. For instance, neurons, muscle cells, and blood cells have distinct intracellular ion compositions. However, there are common patterns observed. The intracellular fluid (ICF) generally has lower [Na+] and higher [K+] compared to the extracellular fluid (ECF). This is primarily due to the activity of the Na+,K+-ATPase, which transports 3 Na+ ions out of the cell and 2 K+ ions into the cell with the hydrolysis of one ATP molecule. The Na+,K+-ATPase not only establishes the Na+ and K+ gradients but also indirectly determines gradients for other ions and molecules. Notably, the K+ gradient generated by the Na+,K+-ATPase activity significantly influences the membrane voltage by allowing K+ to leak out of the cell through K+-selective channels.

Therefore, the Na+,K+-ATPase utilizes ATP energy to establish ion gradients (Na+ and K+) and a voltage gradient (membrane voltage). These ion and electrical gradients generated by the Na+,K+-ATPase drive the transport of various ions and molecules across the cell membrane. For example, several solute carriers facilitate the transport of Na+ along with other ions or molecules. The Na+-glucose and Na+–amino acid symporters utilize the Na+ electrochemical gradient to facilitate the secondary active cellular uptake of glucose and amino acids. Similarly, the inwardly directed Na+ gradient enables the secondary active extrusion of H+ from the cell, contributing to intracellular pH regulation. The 3Na+-Ca++ antiporter, in conjunction with the plasma membrane Ca++-ATPase, expels Ca++ from the cell, maintaining low intracellular [Ca++].

Furthermore, the membrane voltage drives the efflux of Cl− from the cell via Cl−-selective channels, resulting in lower intracellular Cl− concentration compared to the ECF.
Pi1.0-1.4(total)mmol/L 0.5-0.7(ionized)0.5-0.7(ionized) *Ca++ andPi(H2PO4−/HPO4−2)areboundtoproteinsandotherorganicmolecules.Inaddition,largeamountsofCa++ canbesequesteredwithincells.LargeamountsofPiarepresentincellsaspartoforganicmolecules,suchasadenosinetriphosphate(ATP).
composition and cell volume is accomplished through the activity of specific transporters in the plasma membrane of the cells. This section is a review of the mechanisms by which cells maintain their intracellular ionic environment and their membrane potential and by which they control their volume.
Ionic Composition of Cells
The intracellular ionic composition of cells varies from tissue to tissue. For example, the intracellular composition of neurons is different from that of muscle cells, both of which differ from that of blood cells. Nevertheless, there are similar patterns, and these are presented in . In comparison with the ECF, the ICF is characterized by a low [Na+] and a high [K+]. This is the result of the activity of the Na+,K+-ATPase, which transports 3 Na+ ions out of the cell and 2 K+ ions into the cell for each ATP molecule hydrolyzed. As discussed later in this chapter, the activity of the Na+,K+-ATPase not only is important for establishing the cellular Na+ and K+ gradients but also is involved in determining, indirectly, the cellular gradients for many other ions and molecules. Of importance is that the cellular K+ gradient generated by the activity of the Na+,K+-ATPase is a major determinant of the membrane voltage because of the leak of K+ out of the cell through K+selective channels (see the section “
Membrane Potential”).
Thus the Na+,K+-ATPase converts the energy in ATP into ion gradients (i.e., Na+ and K+), and a voltage gradient (i.e., membrane voltage).
The Na+,K+-ATPase–generated ion and electrical gradients are used to drive the transport of other ions and molecules into or out of the cell (
Fig. 2.3 ). For example, as described in , a number of solute carriers couple the transport of Na+ to that of other ions or molecules. The Na+-glucose and Na+–amino acid symporters use the energy in the Na+ electrochemical gradient, directed to bring Na+
CHAPTER 2 Homeostasis: Volume and Composition of Body Fluid Compartments •Fig. 2.3 Cell Model Depicting How Cellular Gradients and the Membrane Potential (Vm) Are Established. (1)TheNa+,K+-ATPasedecreasestheintracellular[Na+]andincreasestheintracellular[K+].SomeK+ exitsthecellviaK+-selectivechannelsandgeneratestheVm(cell’sinterioriselectricallynegative).(2)TheenergyintheNa+ electrochemicalgradientdrivesthetransportofotherionsandmoleculesthroughtheuseofvarioussolutecarriers.(3)TheVmdrivesCl− outofthecellviaCl−-selectivechannels.(4)TheCa++-ATPaseandthe3Na+-Ca++ antiportersmaintainthelowintracellular[Ca++].
into the cell, to drive the secondary active cellular uptake of glucose and amino acids. Similarly, the inwardly directed Na+ gradient drives the secondary active extrusion of H+ from the cell and thus contributes to the maintenance of intracellular pH. The 3Na+-Ca++ antiporter, along with the plasma membrane Ca++-ATPase, extrudes Ca++ from the cell and thus contributes to the maintenance of a low intracellular [Ca++].
In addition, the membrane voltage drives Cl− out of the cell through Cl−-selective channels, thus lowering the intracellular concentration below that of the ECF.