Among the innumerable proteins that support life in its many forms, ion channels are some of the most fascinating, partly for what they do, and partly for how they do it. Endothelial cells (ECs) express a great variety of ion channels. The most obvious function of these channels is to sense chemical and mechanical stimuli, by which they are activated, and to transform these stimuli into changes in ion fluxes. Simply put, in response to stimuli, the ion channels undergo an extremely rapid conformational change that converts an impermeable structure into highly permeable holes in the membrane through which ions can pass.
It appears that the main functions of these channels are to control two vital parameters: Calcium (Ca2+) influx and membrane potential (Figure 79.1). ECs generally are regarded as nonexcitable. Little functional role exists for voltage-gated Ca2+ channels such as the L-type and T-type Ca2+ channels in ECs; these channels play more important roles in myocytes and neurons. In ECs, Ca2+ enters the cells via nonselective cation channels. Ca2+ influx results in a rise in cytosolic Ca2+ level ([Ca2+]i), which in turn controls the production and/or release of numerous vasoactive agents from endothelium. These agents include nitric oxide (NO), endothelium-derived hyperpolarizing factor (EDHF), vasodilatory and vasoconstrictive prostaglandins, endothelins, and tissue-type plasminogen activator (t-PA), and they serve to regulate multiple vascular functions, such as vessel tone, vascular permeability, blood coagulation, and EC growth. In addition to controlling the endothelial [Ca2+]i, endothelial ion channels, especially potassium (K+) and chloride (Cl−) channels, also act to maintain endothelial membrane potential. Membrane potential, together with the transmembrane concentration gradient for Ca2+, provides the electrochemical driving force for transmembrane Ca2+ influx into ECs.