A Short Guide to Electrophysiology and Ion Channels

Abstract

ABSTRACT:The birth and discovery of electrophysiological science took place in the 18 th century laying the path for our understanding of nerve membrane ionic currents. The pore-forming proteins, ion channels, are involved and play critical roles in very important physiological and pathological processes, such as neuronal signaling and cardiac excitability, therefore, they serve as therapeutic drug targets. The study of physiological, pharmacological and biophysical properties of ion channels can be done by patch clamp, a gold standard and powerful electrophysiological technique. The current review, in addition to highlight and cover the history of electrophysiology, patch clamp (conventional and automated) technique, and different types of ion channels, will also discuss the importance of ion channels in different neurological diseases and disorders. As the field of neuroscience is growing, this manuscript is intended as a guide to help in understanding the importance of ion channels, particularly in neuroscience, and also in using the patch clamp technique for the study of molecular physiology, pathophysiology, and pharmacology of neuronal ion channels. Importantly, this review will spotlight on the therapeutic aspect of neuronal ion channels.

Treasure troves of pharmacological tools to study transient receptor potential canonical 1/4/5 channels

“…Ion channels are pore‐forming proteins, which are involved and play critical roles in very important physiological and pathological processes, such as neuronal signalling and cardiac excitability. Therefore, ion channels serve as therapeutic drug targets (Bagal et al, ; Rubaiy, ). The human transient receptor potential (TRP) proteins comprise a family of 27 cation channels that are predominately calcium (Ca 2+ )‐permeable (Nilius & Szallasi, ).…”

“…It is worth mentioning that the function of TRPC1 is a matter of debate, as when expressed alone, it does not form a functional ion channel (Beech, ; Rubaiy, Ludlow, Henrot, et al, ). For the past two decades, a plethora of studies have reported that the TRPC channels play vital roles in many physiological and pathological mechanisms (Beech, ; Nilius & Szallasi, ; Rubaiy, ).…”

“…The transport of ions across the cell membrane plays a vital role in normal cell functions (Clapham, ; Rubaiy, ). The Ca 2+ ion is a universal second messenger that regulates a wide variety of very important functions in almost all cell types (Clapham, ).…”

“…At present, it is well documented that [Ca 2+ ] i homeostasis is altered in cancer cells and that a dysregulation of Ca 2+ signalling plays a role in tumour initiation, progression, metastasis, and angiogenesis. Therefore, the targeting Ca 2+ signalling and nonselective calcium permeable TRP channels have become an emerging research field for cancer therapy (Gaunt, Vasudev, & Beech, ; Liberati, Morelli, Nabissi, Santoni, & Santoni, ; Rubaiy, ). However, in this review, we will focus on the involvement of TRPC1/4/5 channels in cancer and their potential therapeutic target by using small molecules, such as (−)‐englerin A (EA) and tonantzitlolone (TZL; Gaunt et al, ; Minard et al, ; Rubaiy, Ludlow, et al, ; Sourbier et al, ).…”

Identification of an (−)‐englerin A analogue, which antagonizes (−)‐englerin A at TRPC1/4/5 channels

“…The transient receptor potential canonical (TRPC) proteins are a subfamily of the TRP superfamily and assemble as homo and heterotetramers to form Ca 2+ ‐permeable non‐selective cationic channels (Abramowitz and Birnbaumer, ; Beech, ; Damann et al ., ; Gaunt et al ., ; Moran et al ., ; Rubaiy, ). They appear to function in two clusters, TRPC1 / TRPC4 / TRPC5 and TRPC3/TRPC6/TRPC7, which are distinguishable pharmacologically (Akbulut et al ., ; Bon and Beech, ; Maier et al ., ; Miller et al ., ; Washburn et al ., ; Rubaiy et al ., ,b).…”