Year: 1993
Type: article
Abstract: J on channels are pore-forming macromolecules that provide a passive conduit for ion transfer across membranes.Although simple ionophores such as gramicidin and nystatin' fall within this legalistic defi- nition, the ion channels of eukaryotic cells are integral membrane proteins, many of which have now been isolated biochemically, reconstituted, cloned, and ex- pressed.These fascinating proteins play a particularly prominent role in the function of the cardiovascular system by conferring excitability in an exquisitely tissue- specific manner and by mediating a number of key steps in signal transduction.The ion channels in a nodal cell enable it to pace, whereas those in a myocyte enable it to contract.In addition to mediating ionic fluxes across cell membranes, ion channels are the primary receptors for a variety of clinically important drugs including antiarrhythmic agents and calcium channel antagonists.'Therefore, it is of considerable interest to cardiovascular biologists to consider how ion channels work.Two distinct sets of properties characterize each type of ion channel: those that determine whether the channel is open or closed, collectively known as the "gating" properties, and those that define just how the channel moves ions when it is open, known as the "permeation" properties.The structure-function correlation of volt- age-gated ion channels is the subject of several general reviews.The present Mini Review focuses specifically on the mechanism of permeation in ion channels, with particular emphasis on the structural domains that form the pore, determine selectivity, and interact with pore- blocking molecules. Development of Molecular Approachesto the Study of Ion Channels Cloning of the voltage-dependent Na+ channel from the electric organ of Electrophorus electricus in 19842 heralded a new era in electrophysiology.The availabil- ity of cDNA for ion channels enabled systematic analysis of structure by mutagenesis and heterologous expression.Since then, ion channels of many classes have been cloned, sequenced, and functionally ex- pressed.(Ironically, the original eel Na+ channel has
Source: Circulation Research
Authors: G F Tomaselli, P H Backx, E Marban
Institutions: Johns Hopkins University, Johns Hopkins Medicine
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W2032109518