Stretch-activated channels in the heart: Their role in arrhythmias and potential as antiarrhythmic drug targets

Abstract

<jats:title>Abstract</jats:title><jats:p>Stretching the myocardium can have profound effects on its electrical activity, a process called mechanoelectric feedback. Mechanoelectric feedback can be powerful enough to trigger arrhythmias, and it is likely to be the underlying trigger for some clinically intractable arrhythmias. It seems likely that the response to stretch involves at least two types of mechanosensitive ion channels, a nonspecific cation channel, and a potassium channel (or channels). Currents carried by nonspecific cation channels have been well characterised in cardiac tissue, although the gene has not yet been identified. Very recently, a peptide toxin isolated from <jats:italic>Grammastola spatulata</jats:italic> has been shown to block this channel and to be an effective antiarrhythmic agent against stretch‐induced atrial arrhythmias. Stretch‐activated potassium currents and single channels have also been recorded in cardiac cells; in the case of these channels, the genes coding for them have recently been cloned and shown to be members of a new potassium channel gene family, the “tandem pore” channels. Although some nonspecific activators and blockers of these channels exist, there is at present no specific blocker, which limits investigation of the role of these channels in arrhythmogenesis. The potential for the development of blockers of both types of stretch‐activated channels as therapeutic agents is discussed. Drug Dev. Res. 55:53–58, 2002. © 2002 Wiley‐Liss, Inc.</jats:p>