Part 2 book “General and molecular pharmacology” has contents: Control of drug plasma concentration, drug–receptor interactions- quantitative and qualitative aspects, receptors and modulation of their response, adaptation to drug response and drug dependence, pharmacological modulation of posttranslational modifications, calcium homeostasis within the cells, and other contents. | SECTION 7 PHARMACOLOGICAL CONTROL OF MEMBRANE TRANSPORT 27 ION CHANNELS Maurizio Taglialatela and Enzo Wanke By reading this chapter, you will: • Become familiar with the main principles governing function, structural organization, and classification of ion channels • Know the role(s) played by the main classes of ion channels in different organs, tissues, and cells • Know the clinical applications of drugs interfering with the function of each ion channel class • Learn how functional changes resulting from drug‐ induced modulation of ion channels can be exploited for therapeutic purposes ION CHANNELS AND TRANSPORTERS Eukaryotic cells use about 30% of their energy to maintain the transmembrane gradients of protons (H+), sodium (Na+), potassium (K+), chloride (Cl−), and calcium (Ca2+), an indi cation of their paramount importance for cell survival and replication. On purely thermodynamic grounds, transmembrane trans port mechanisms can be classified into active and passive. Passive processes transport ions from the side of the mem brane with high electrochemical potential to the side with low electrochemical potential. Two types of proteins are responsible for passive ion transport: facilitated transporters and ion channels (Fig. ), with very different transport mechanisms. Substrate binding to the transporter on one side of the membrane induces a conformational change, resulting in exposure of the substrate on the opposite side of the membrane. The substrate concentration gradient provides the energy required for the process; as the substrate movement is coupled to a conformational change of the transporter, the transfer rate is rather low. By contrast, ion channels contain aqueous pores through which permeating ions can flow at very high rates (>106/s, close to the diffusion rate in water), thus generating significant currents that may rapidly change the resting membrane potential (VREST) of a cell. Both these passive processes dissipate the energy
