Transient Receptor Potential and K+ channel Heteromerization: How to mix and match for new properties

Ion channels are essential proteins that control a huge diversity of physiological processes. Structurally, they are formed from multiple subunits that function together as multimers. Usually, the multimers consist of several identical subunits (homomers), although heteromerization – the formation of multimers from different subunits – is also possible and has been characterized for more than one class of ion channels. The methods employed for the study of heteromerization are diverse. First, the presence of these hybrids can be confirmed by using specific antibodies, labeling techniques or advanced microscopy. Their biophysical characterization can be made possible through the use of varied heterologous expression methods or by constructing complex DNA plasmids, known as concatemers, that encompass all the distinct subunits, leading to the fusion of the different subunits comprising the putative heteromeric channel. Finally, the heteromeric channels are investigated using pharmacological and electrophysiological approaches. Transient receptor potential (TRP) channels play a crucial role in sensory transduction in the peripheral nervous system, being critically involved in pain and temperature sensing. In addition, different members of this family have been identified throughout the body, playing various roles in different tissues. Even though most TRP channels seem to form homomers, several studies have identified and confirmed heteromeric complexes with diverse properties. Similar findings have been reported for several types of potassium channels. This work aims to describe in detail the methods employed in studying heteromeric ion channels and to provide an updated perspective on the latest findings regarding this topic – focusing on TRP and potassium channels.