Conventional Patch Clamp Techniques and High-Throughput Patch Clamp Recordings on a Chip for Measuring Ion Channel Activity

The term “channelopathy” refers to a disease whose primary underlying mechanism(s) involve dysfunctional ion channel activity. Long QT syndrome and cystic fibrosis are two prime examples of channelopathies, where altered transport of K+, Na+, and/or Cl− ions, respectively, leads to pathogenesis. Such findings have aimed a new spotlight at the overall physiological relevance of transmembrane ion flux in disease development and became of critical importance to industry with discoveries that many drugs can unintentionally induce various channelopathies such as epileptic seizures (often from inhibition of neuronal human NaV1.1 Na+ channels), or torsade de pointes (a lethal long QT syndrome produced most often by inhibition of cardiac human ERG K+ channels). As discussed extensively elsewhere in this monograph, ion channels with selective permeability to Na+, K+, and Ca2+ ions modulate pulmonary vasoreactivity, remodeling, and vascular permeability. Although biochemical and molecular biology techniques have contributed, a significant proportion of our knowledge of the role of ion channels in pulmonary physiology has been garnered by measuring transmembrane ionic currents in intact cells using patch clamp electrophysiology. The purpose of this chapter is to introduce the basics of conventional and high-throughput patch clamp technology and how this can be used to advance the research into the cause of pulmonary vascular diseases.